Editing Cerebral cortex

{{Short description|Outer layer of the cerebrum of the mammalian brain}}
{{For-multi|the scientific journal|Cerebral Cortex (journal)|the cerebellar cortex|Cerebellum#Gross anatomy}}
{{Use dmy dates|date=May 2024}}
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{{Infobox brain
| Name            = Cerebral cortex
| Latin           = cortex cerebri
| Image           = Cerebral cortex, side view.svg| 
| Caption         = The [[Sulcus (neuroanatomy)|sulci]] and [[Gyrus|gyri]] (folds and ridges) of the cortex
| Image2          = Blausen 0103 Brain Sensory&Motor.png
| Caption2        = Motor and sensory areas of the cerebral cortex
| IsPartOf        = [[Cerebrum]]
| Components      =
| Artery          =
| Vein            =
| Acronym         =
}}

The '''cerebral cortex''', also known as the '''cerebral mantle''',<ref name="free">{{cite web |title=cerebral mantle |url=https://www.thefreedictionary.com/cerebral+mantle |website=TheFreeDictionary.com|access-date=9 May 2024}}</ref> is the outer layer of [[neural tissue]] of the [[cerebrum]] of the [[brain]] in [[humans]] and other [[mammal]]s. It is the largest site of [[Neuron|neural integration]] in the [[central nervous system]],<ref name="Saladin"/> and plays a key role in [[attention]], [[perception]], [[awareness]], [[thought]], [[memory]], [[language]], and [[consciousness]].

The six-layered [[neocortex]] makes up approximately 90% of the [[Cortex (anatomy)|cortex]], with the [[allocortex]] making up the remainder.<ref name="Strominger">{{cite book | vauthors = Strominger NL, Demarest RJ, Laemle LB |title=Noback's Human Nervous System | edition = Seventh |chapter=Cerebral Cortex |publisher=Humana Press |pages=429–451 |language=en |doi=10.1007/978-1-61779-779-8_25 |date=2012 |isbn=978-1-61779-778-1}}</ref> The cortex is divided into left and right parts by the [[longitudinal fissure]], which separates the two [[cerebral hemisphere]]s that are joined beneath the cortex by the [[corpus callosum]] and other [[commissural fibers]]. In most mammals, apart from small mammals that have small brains, the cerebral cortex is folded, providing a greater surface area in the confined volume of the [[neurocranium|cranium]]. Apart from minimising brain and cranial volume, [[gyrification|cortical folding]] is crucial for the [[Neural circuit|brain circuitry]] and its functional organisation.<ref name="Shipp_2007"/> In mammals with small brains, there is no folding and the cortex is smooth.<ref name="embo">{{cite journal | vauthors = Fernández V, Llinares-Benadero C, Borrell V | title = Cerebral cortex expansion and folding: what have we learned? | journal = The EMBO Journal | volume = 35 | issue = 10 | pages = 1021–1044 | date = May 2016 | pmid = 27056680 | pmc = 4868950 | doi = 10.15252/embj.201593701 }}</ref><ref name="ReferenceA">{{cite journal | vauthors = Rakic P | title = Evolution of the neocortex: a perspective from developmental biology | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 10 | pages = 724–735 | date = October 2009 | pmid = 19763105 | pmc = 2913577 | doi = 10.1038/nrn2719 }}</ref>

A fold or ridge in the cortex is termed a [[gyrus]] (plural gyri) and a groove is termed a [[Sulcus (neuroanatomy)|sulcus]] (plural sulci). These surface convolutions appear during [[prenatal development|fetal development]] and continue to mature after birth through the process of [[gyrification]]. In the [[human brain]], the majority of the cerebral cortex is not visible from the outside, but buried in the sulci.<ref name="Principles of Neural Science">{{cite book |title=Principles of neural science |publisher=McGraw-Hill, Health Professions Division |isbn=978-0-8385-7701-1 |edition=4th |date=2000-01-05 |url-access=registration |url=https://archive.org/details/isbn_9780838577011}}</ref> The major sulci and gyri mark the divisions of the cerebrum into the [[lobes of the brain]]. The four major lobes are the [[Frontal lobe|frontal]], [[Parietal lobe|parietal]], [[Occipital lobe|occipital]] and [[temporal lobe|temporal]] lobes. Other lobes are the [[limbic lobe]], and the [[insular cortex]] often referred to as the ''insular lobe''.

There are between 14 and 16 billion [[neuron]]s in the human cerebral cortex.<ref name="Saladin"/> These are organised into horizontal cortical layers, and radially into [[cortical column]]s and [[minicolumn]]s. Cortical areas have specific functions such as movement in the [[motor cortex]], and sight in the [[visual cortex]]. The motor cortex is primarily located in the [[Primary motor cortex|precentral gyrus]], and the visual cortex is located in the occipital lobe.

== Structure ==
[[File:Human motor cortex.jpg|thumb|Lateral view of cerebrum showing several cortices]]

The cerebral cortex is the outer covering of the surfaces of the cerebral hemispheres and is folded into peaks called [[gyrus|gyri]], and grooves called [[Sulcus (neuroanatomy)|sulci]]. In the [[human brain]], it is between 2 and 3-4 mm. thick,<ref name="Roberts">{{cite book | vauthors = Roberts P |title=Neuroanatomy |date=1992 |publisher=Springer-Verlag |isbn=978-0-387-97777-5 |pages=86–92 |edition=3rd}}</ref> and makes up 40% of the brain's mass.<ref name="Saladin">{{cite book | vauthors = Saladin K |title=Human anatomy |date=2011 |publisher=McGraw-Hill |isbn=978-0-07-122207-5 |pages=416–422 |edition=3rd}}</ref> 90% of the cerebral cortex is the six-layered [[neocortex]] whilst the other 10% is made up of the three/four-layered [[allocortex]].<ref name="Saladin"/> There are between 14 and 16 billion neurons in the cortex.<ref name="Saladin"/> These cortical neurons are organized radially in [[cortical column]]s, and [[cortical minicolumn|minicolumns]], in the horizontally organized layers of the cortex.<ref name="Lodato">{{cite journal | vauthors = Lodato S, Arlotta P | title = Generating neuronal diversity in the mammalian cerebral cortex | journal = Annual Review of Cell and Developmental Biology | volume = 31 | issue = 1 | pages = 699–720 | date = 2015-11-13 | pmid = 26359774 | pmc = 4778709 | doi = 10.1146/annurev-cellbio-100814-125353 | quote = Functional columns were first defined in the cortex by Mountcastle (1957), who proposed the columnar hypothesis, which states that the cortex is composed of discrete, modular columns of neurons, characterized by a consistent connectivity profile. }}</ref><ref name="Ansen-Wilson">{{cite journal | vauthors = Ansen-Wilson LJ, Lipinski RJ | title = Gene-environment interactions in cortical interneuron development and dysfunction: A review of preclinical studies | journal = Neurotoxicology | volume = 58 | pages = 120–129 | date = January 2017 | pmid = 27932026 | pmc = 5328258 | doi = 10.1016/j.neuro.2016.12.002 | bibcode = 2017NeuTx..58..120A }}</ref>

The neocortex is separable into different regions of cortex known in the plural as cortices, and include the [[motor cortex]] and [[visual cortex]]. About two thirds of the cortical surface is buried in the sulci and the [[insular cortex]] is completely hidden. The cortex is thickest over the top of a gyrus and thinnest at the bottom of a sulcus.<ref name="Carpenter">{{cite book | vauthors = Carpenter MB |title=Core text of neuroanatomy |date=1985 |publisher=Williams & Wilkins |isbn=978-0-683-01455-6 |pages=348–358 |edition=3rd}}</ref>

===Folds===
{{Further |Gyrification}}
The cerebral cortex is folded in a way that allows a large surface area of [[nervous tissue|neural tissue]] to fit within the confines of the [[neurocranium]]. When unfolded in the human, each [[cerebral hemisphere|hemispheric]] cortex has a total surface area of about {{convert|0.12|sqm}}.<ref>{{cite journal | vauthors = Toro R, Perron M, Pike B, Richer L, Veillette S, Pausova Z, Paus T | title = Brain size and folding of the human cerebral cortex | journal = Cerebral Cortex | volume = 18 | issue = 10 | pages = 2352–2357 | date = October 2008 | pmid = 18267953 | doi = 10.1093/cercor/bhm261 | doi-access = free }}</ref> The folding is inward away from the surface of the brain, and is also present on the medial surface of each hemisphere within the [[longitudinal fissure]]. Most mammals have a cerebral cortex that is convoluted with the peaks known as gyri and the troughs or grooves known as sulci. Some small mammals including some small [[rodent]]s have smooth cerebral surfaces without [[gyrification]].<ref name="ReferenceA"/>

===Lobes===
{{See also|Lobes of the brain}}
The larger sulci and gyri mark the divisions of the cortex of the cerebrum into the [[lobes of the brain]].<ref name="Roberts"/> There are four main lobes: the [[frontal lobe]], [[parietal lobe]], [[temporal lobe]], and [[occipital lobe]]. The [[insular cortex]] is often included as the insular lobe.<ref name="Nieuwenhuys">{{cite book | vauthors = Nieuwenhuys R |chapter=The insular cortex |title=Evolution of the Primate Brain |series=Progress in Brain Research |date=2012 |volume=195 |pages=123–63 |doi=10.1016/B978-0-444-53860-4.00007-6 |pmid=22230626|isbn=978-0-444-53860-4 }}</ref> The [[limbic lobe]] is a rim of cortex on the medial side of each hemisphere and is also often included.<ref name="Wiley">{{cite book | vauthors = Tortora G, Derrickson B |title=Principles of anatomy & physiology. |date=2011 |publisher=Wiley |isbn=978-0-470-64608-3 |page=549 |edition=13th.}}</ref> There are also three lobules of the brain described: the [[paracentral lobule]], the [[superior parietal lobule]], and the [[inferior parietal lobule]].

===Thickness===
For species of mammals, larger brains (in absolute terms, not just in relation to body size) tend to have thicker cortices.<ref name=CNSVert/> The smallest mammals, such as [[shrew]]s, have a neocortical thickness of about 0.5&nbsp;mm; the ones with the largest brains, such as humans and fin whales, have thicknesses of 2–4&nbsp;mm.<ref name="Saladin"/><ref name="Roberts"/> There is an approximately [[logarithm]]ic relationship between brain weight and cortical thickness.<ref name=CNSVert>{{cite book |title=The central nervous system of vertebrates, Volume 1 |publisher=Springer |year=1998 |isbn=978-3-540-56013-5 |pages=2011–2012 |vauthors=Nieuwenhuys R, Donkelaar HJ, Nicholson C}}</ref>
[[Magnetic resonance imaging of the brain]] (MRI) makes it possible to get a measure for the thickness of the human cerebral cortex and relate it to other measures. The thickness of different cortical areas varies but in general, sensory cortex is thinner than motor cortex.<ref>{{cite journal | vauthors = Kruggel F, Brückner MK, Arendt T, Wiggins CJ, von Cramon DY | title = Analyzing the neocortical fine-structure | journal = Medical Image Analysis | volume = 7 | issue = 3 | pages = 251–264 | date = September 2003 | pmid = 12946467 | doi = 10.1016/S1361-8415(03)00006-9 | hdl-access = free | hdl = 11858/00-001M-0000-0010-9C60-3 }}</ref> One study has found some positive association between the cortical thickness and [[intelligence]].<ref>{{cite journal | vauthors = Narr KL, Woods RP, Thompson PM, Szeszko P, Robinson D, Dimtcheva T, Gurbani M, Toga AW, Bilder RM | title = Relationships between IQ and regional cortical gray matter thickness in healthy adults | journal = Cerebral Cortex | volume = 17 | issue = 9 | pages = 2163–2171 | date = September 2007 | pmid = 17118969 | doi = 10.1093/cercor/bhl125 | doi-access = free }}</ref>
Another study has found that the [[somatosensory cortex]] is thicker in [[migraine]] patients, though it is not known if this is the result of migraine attacks, the cause of them or if both are the result of a shared cause.<ref>{{cite journal | vauthors = DaSilva AF, Granziera C, Snyder J, Hadjikhani N | title = Thickening in the somatosensory cortex of patients with migraine | journal = Neurology | volume = 69 | issue = 21 | pages = 1990–1995 | date = November 2007 | pmid = 18025393 | pmc = 3757544 | doi = 10.1212/01.wnl.0000291618.32247.2d }}</ref><ref>{{cite news | vauthors = Paddock C |title=Migraine Sufferers Have Thicker Brain Cortex |work=[[Medical News Today]] |url=http://www.medicalnewstoday.com/articles/89286.php |date=2007-11-20| url-status = live| archive-url = https://web.archive.org/web/20080511153657/http://www.medicalnewstoday.com/articles/89286.php| archive-date = 2008-05-11}}</ref>
A later study using a larger patient population reports no change in the cortical thickness in patients with migraine.<ref>{{cite journal | vauthors = Datta R, Detre JA, Aguirre GK, Cucchiara B | title = Absence of changes in cortical thickness in patients with migraine | journal = Cephalalgia | volume = 31 | issue = 14 | pages = 1452–1458 | date = October 2011 | pmid = 21911412 | pmc = 3512201 | doi = 10.1177/0333102411421025 }}</ref>
A genetic disorder of the cerebral cortex, whereby decreased folding in certain areas results in a [[microgyrus]], where there are four layers instead of six, is in some instances seen to be related to [[dyslexia]].<ref>{{cite journal | vauthors = Habib M | title = The neurological basis of developmental dyslexia: an overview and working hypothesis | journal = Brain | volume = 123 Pt 12 | issue = 12 | pages = 2373–2399 | date = December 2000 | pmid = 11099442 | doi = 10.1093/brain/123.12.2373 | doi-access = free }}</ref>

=== {{anchor|Layers}}{{anchor|Laminar pattern}}Layers of neocortex ===
[[File:Minute structure of the cerebral cortex.jpg|thumb|Diagram of layers pattern. Cells grouped on left, axonal layers on right.]]
[[File:Cajal cortex drawings.png|thumb|right|Three drawings of cortical lamination by [[Santiago Ramon y Cajal]], each showing a vertical cross-section, with the surface of the cortex at the top. Left: [[Nissl stain|Nissl]]-stained visual cortex of a human adult. Middle: Nissl-stained motor cortex of a human adult. Right: [[Golgi stain|Golgi]]-stained cortex of a {{frac|1|1|2}} month-old infant. The Nissl stain shows the cell bodies of neurons; the Golgi stain shows the [[dendrite]]s and axons of a random subset of neurons.]]
[[File:Visual cortex - low mag.jpg|thumb|[[Micrograph]] showing the [[visual cortex]] (predominantly pink). Subcortical [[white matter]] (predominantly blue) is seen at the bottom of the image. [[LFB stain|HE-LFB stain]].]]
[[File:NeuronGolgi.png|thumb|[[Golgi's method|Golgi-stained]] neurons in the cortex ([[macaque]])]]

The [[neocortex]] is formed of six layers, numbered I to VI, from the outermost layer I – near to the [[pia mater]], to the innermost layer VI – near to the underlying [[white matter]]. Each cortical layer has a characteristic distribution of different neurons and their connections with other cortical and subcortical regions. There are direct connections between different cortical areas and indirect connections via the thalamus.

One of the clearest examples of [[laminar organization|cortical layering]] is the [[line of Gennari]] in the [[Visual cortex#Primary visual cortex (V1)|primary visual cortex]]. This is a band of whiter tissue that can be observed with the naked eye in the [[calcarine sulcus]] of the occipital lobe. The line of Gennari is composed of [[axon]]s bringing visual information from the [[thalamus]] into layer IV of the [[visual cortex]].

[[Staining]] cross-sections of the cortex to reveal the position of neuronal cell bodies and the intracortical axon tracts allowed neuroanatomists in the early 20th century to produce a detailed description of the ''laminar structure of the cortex'' in different species. The work of [[Korbinian Brodmann]] (1909) established that the mammalian neocortex is consistently divided into six layers.

====Layer I====
{{See also|Core-matrix theory of thalamus}}
Layer I is the '''molecular layer''', and contains few scattered neurons, including [[GABAergic]] [[rosehip neuron]]s.<ref name="Allen">{{cite web |title=Scientists identify a new kind of human brain cell |url=https://www.alleninstitute.org/what-we-do/brain-science/news-press/articles/scientists-identify-new-kind-human-brain-cell |website=Allen Institute |date=27 August 2018}}</ref> Layer I consists largely of extensions of apical [[dendrite|dendritic]] tufts of [[pyramidal cell|pyramidal neurons]] and horizontally oriented axons, as well as [[glial cells]].<ref name="Shipp_2007">{{cite journal | vauthors = Shipp S | title = Structure and function of the cerebral cortex | journal = Current Biology | volume = 17 | issue = 12 | pages = R443–R449 | date = June 2007 | pmid = 17580069 | pmc = 1870400 | doi = 10.1016/j.cub.2007.03.044 | bibcode = 2007CBio...17.R443S }}</ref> During development, [[Cajal–Retzius cell]]s<ref>{{cite journal | vauthors = Meyer G, Goffinet AM, Fairén A | title = What is a Cajal-Retzius cell? A reassessment of a classical cell type based on recent observations in the developing neocortex | journal = Cerebral Cortex | volume = 9 | issue = 8 | pages = 765–775 | date = December 1999 | pmid = 10600995 | doi = 10.1093/cercor/9.8.765 | doi-access =  }}</ref> and subpial granular layer cells<ref>{{cite journal | vauthors = Judaš M, Pletikos M |title=The discovery of the subpial granular layer in the human cerebral cortex |journal=Translational Neuroscience |date=2010 |volume=1 |issue=3 |pages=255–260 |doi=10.2478/v10134-010-0037-4 |s2cid=143409890|doi-access=free }}</ref> are present in this layer. Also, some spiny [[stellate cells]] can be found here. Inputs to the apical tufts are thought to be crucial for the ''feedback'' interactions in the cerebral cortex involved in associative learning and attention.<ref>{{cite journal | vauthors = Gilbert CD, Sigman M | title = Brain states: top-down influences in sensory processing | journal = Neuron | volume = 54 | issue = 5 | pages = 677–696 | date = June 2007 | pmid = 17553419 | doi = 10.1016/j.neuron.2007.05.019 | hdl-access = free | doi-access = free | hdl = 11336/67502 }}</ref>

While it was once thought that the input to layer I came from the cortex itself,<ref>{{cite journal | vauthors = Cauller L | title = Layer I of primary sensory neocortex: where top-down converges upon bottom-up | journal = Behavioural Brain Research | volume = 71 | issue = 1–2 | pages = 163–170 | date = November 1995 | pmid = 8747184 | doi = 10.1016/0166-4328(95)00032-1 | s2cid = 4015532 }}</ref> it is now known that layer I across the cerebral cortex receives substantial input from ''matrix'' or M-type thalamus cells,<ref>{{cite journal | vauthors = Rubio-Garrido P, Pérez-de-Manzo F, Porrero C, Galazo MJ, Clascá F | title = Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent | journal = Cerebral Cortex | volume = 19 | issue = 10 | pages = 2380–2395 | date = October 2009 | pmid = 19188274 | doi = 10.1093/cercor/bhn259 | doi-access = free }}</ref> as opposed to ''core'' or C-type that go to layer IV.<ref name="Jones">{{cite journal | vauthors = Jones EG | title = Viewpoint: the core and matrix of thalamic organization | journal = Neuroscience | volume = 85 | issue = 2 | pages = 331–345 | date = July 1998 | pmid = 9622234 | doi = 10.1016/S0306-4522(97)00581-2 | s2cid = 17846130 }}</ref>

It is thought that layer I serves as a central hub for collecting and processing widespread information. It integrates ascending sensory inputs with top-down expectations, regulating how sensory perceptions align with anticipated outcomes. Further, layer I sorts, directs, and combines excitatory inputs, integrating them with neuromodulatory signals. Inhibitory interneurons, both within layer I and from other cortical layers, gate these signals. Together, these interactions dynamically calibrate information flow throughout the neocortex, shaping perceptions and experiences.<ref name="s309">{{cite journal | vauthors = Huang S, Wu SJ, Sansone G, Ibrahim LA, Fishell G | title = Layer 1 neocortex: Gating and integrating multidimensional signals | journal = Neuron | volume = 112 | issue = 2 | pages = 184–200 | date = January 2024 | pmid = 37913772 | doi = 10.1016/j.neuron.2023.09.041 | pmc = 11180419 }}</ref>

====Layer II====
Layer II, the '''[[External granular layer (cerebral cortex)|external granular layer]]''', contains small [[Pyramidal cell|pyramidal neurons]] and numerous stellate neurons.

====Layer III====
Layer III, the '''external pyramidal layer''', contains predominantly small and medium-size pyramidal neurons, as well as non-pyramidal neurons with vertically oriented intracortical axons; layers I through III are the main target of [[commissural fiber|commissural]] corticocortical [[afferent nerve fiber|afferents]], and layer III is the principal source of corticocortical [[efferent nerve fiber|efferents]].

====Layer IV====
Layer IV, the '''[[internal granular layer]]''', contains different types of [[stellate cell|stellate]] and pyramidal cells, and is the main target of [[thalamocortical radiations|thalamocortical afferents]] from thalamus type C neurons (core-type)<ref name="Jones"/> as well as intra-hemispheric corticocortical afferents. The layers above layer IV are also referred to as supragranular layers (layers I-III), whereas the layers below are referred to as infragranular layers (layers V and VI). [[African elephant|African elephants]], [[Cetacea|cetaceans]], and [[hippopotamus]] do not have a layer IV with axons which would terminate there going instead to the inner part of layer III.<ref name="u035">{{cite journal | vauthors = Bhagwandin A, Molnár Z, Bertelsen MF, Karlsson KÆ, Alagaili AN, Bennett NC, Hof PR, Kaswera-Kyamakya C, Gilissen E, Jayakumar J, Manger PR | title = Where Do Core Thalamocortical Axons Terminate in Mammalian Neocortex When There Is No Cytoarchitecturally Distinct Layer 4? | journal = The Journal of Comparative Neurology | volume = 532 | issue = 7 | pages = e25652 | date = July 2024 | pmid = 38962882 | doi = 10.1002/cne.25652 }}</ref> 

====Layer V====
Layer V, the '''internal pyramidal layer''', contains large pyramidal neurons. Axons from these leave the cortex and connect with subcortical structures including the [[basal ganglia]]. In the primary motor cortex of the frontal lobe, layer V contains giant pyramidal cells called [[Betz cell]]s, whose axons travel through the [[internal capsule]], the [[brain stem]], and the spinal cord forming the [[corticospinal tract]], which is the main pathway for voluntary motor control.

====Layer VI====
Layer VI, the '''polymorphic layer''' or '''multiform layer''', contains few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons; layer VI sends [[Efferent nerve fiber|efferent fibers]] to the thalamus, establishing a very precise reciprocal interconnection between the cortex and the thalamus.<ref>Creutzfeldt, O. 1995. ''Cortex Cerebri''. Springer-Verlag.</ref> That is, layer VI neurons from one cortical column connect with thalamus neurons that provide input to the same cortical column. These connections are both excitatory and inhibitory. Neurons send [[Excitatory postsynaptic potential|excitatory]] fibers to neurons in the thalamus and also send collaterals to the [[thalamic reticular nucleus]] that [[Inhibitory postsynaptic potential|inhibit]] these same thalamus neurons or ones adjacent to them.<ref name="Lam">{{cite journal | vauthors = Lam YW, Sherman SM | title = Functional organization of the somatosensory cortical layer 6 feedback to the thalamus | journal = Cerebral Cortex | volume = 20 | issue = 1 | pages = 13–24 | date = January 2010 | pmid = 19447861 | pmc = 2792186 | doi = 10.1093/cercor/bhp077 }}</ref> One theory is that because the inhibitory output is reduced by [[cholinergic]] input to the cerebral cortex, this provides the [[brainstem]] with adjustable "gain control for the relay of [[Posterior column-medial lemniscus pathway|lemniscal]] inputs".<ref name="Lam"/>

===Columns===
The cortical layers are not simply stacked one over the other; there exist characteristic connections between different layers and neuronal types, which span all the thickness of the cortex. These cortical microcircuits are grouped into [[cortical column]]s and [[Cortical minicolumn|minicolumns]].<ref name="Suzuki">{{cite journal | vauthors = Suzuki IK, Hirata T | title = Neocortical neurogenesis is not really "neo": a new evolutionary model derived from a comparative study of chick pallial development | journal = Development, Growth & Differentiation | volume = 55 | issue = 1 | pages = 173–187 | date = January 2013 | pmid = 23230908 | doi = 10.1111/dgd.12020 | s2cid = 36706690 | doi-access = free }}</ref> It has been proposed that the minicolumns are the basic functional units of the cortex.<ref>{{cite journal | vauthors = Mountcastle VB | title = The columnar organization of the neocortex | journal = Brain | volume = 120 ( Pt 4) | issue = 4 | pages = 701–722 | date = April 1997 | pmid = 9153131 | doi = 10.1093/brain/120.4.701 | doi-access = free }}</ref> In 1957, [[Vernon Benjamin Mountcastle|Vernon Mountcastle]] showed that the functional properties of the cortex change abruptly between laterally adjacent points; however, they are continuous in the direction perpendicular to the surface. Later works have provided evidence of the presence of functionally distinct cortical columns in the visual cortex (Hubel and [[Torsten Wiesel|Wiesel]], 1959),<ref name="pmid14403679">{{cite journal | vauthors = Hubel DH, Wiesel TN | title = Receptive fields of single neurones in the cat's striate cortex | journal = The Journal of Physiology | volume = 148 | issue = 3 | pages = 574–591 | date = October 1959 | pmid = 14403679 | pmc = 1363130 | doi = 10.1113/jphysiol.1959.sp006308 }}</ref> auditory cortex,
and associative cortex.

Cortical areas that lack a layer IV are called [[agranular cortex|agranular]]. Cortical areas that have only a rudimentary layer IV are called dysgranular.<ref>S.M. Dombrowski, C.C. Hilgetag, and H. Barbas. [http://cercor.oxfordjournals.org/cgi/content/full/11/10/975 Quantitative Architecture Distinguishes Prefrontal Cortical Systems in the Rhesus Monkey] {{webarchive|url=https://web.archive.org/web/20080829143033/http://cercor.oxfordjournals.org/cgi/content/full/11/10/975 |date=2008-08-29 }}.Cereb. ''Cortex'' 11: 975–988. "...they either lack (agranular) or have only a rudimentary granular layer IV (dysgranular)."</ref> Information processing within each layer is determined by different temporal dynamics with that in layers II/III having a slow 2&nbsp;[[Hertz|Hz]] [[Neural oscillation|oscillation]] while that in layer V has a fast 10–15&nbsp;Hz oscillation.<ref>{{cite journal | vauthors = Sun W, Dan Y | title = Layer-specific network oscillation and spatiotemporal receptive field in the visual cortex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 42 | pages = 17986–17991 | date = October 2009 | pmid = 19805197 | pmc = 2764922 | doi = 10.1073/pnas.0903962106 | doi-access = free | bibcode = 2009PNAS..10617986S }}</ref>

===Types of cortex===

Based on the differences in [[laminar organization]] the cerebral cortex can be classified into two types, the large area of [[neocortex]] which has six cell layers, and the much smaller area of [[allocortex]] that has three or four layers:<ref name="Strominger"/>

* The neocortex is also known as the isocortex or neopallium and is the part of the mature cerebral cortex with six distinct layers. Examples of neocortical areas include the granular [[primary motor cortex]], and the striate [[primary visual cortex]]. The neocortex has two subtypes, the ''true isocortex'' and the [[proisocortex]] which is a transitional region between the isocortex and the regions of the periallocortex.
* The allocortex is the part of the cerebral cortex with three or four layers, and has three subtypes, the [[paleocortex]] with three cortical laminae, the [[archicortex]] which has four or five, and a transitional area adjacent to the allocortex, the [[periallocortex]]. Examples of allocortex are the [[olfactory cortex]] and the [[hippocampus]].

There is a transitional area between the neocortex and the allocortex called the [[paralimbic cortex]], where layers 2, 3 and 4 are merged. This area incorporates the proisocortex of the neocortex and the periallocortex of the allocortex. In addition, the cerebral cortex may be classified into four [[Lobes of the brain|lobes]]: the [[frontal lobe]], [[temporal lobe]], the [[parietal lobe]], and the [[occipital lobe]], named from their overlying bones of the skull.

==Blood supply and drainage==
{{Main|Cerebral circulation}}
[[File:Cerebrovascular System.png|thumb|Arterial supply showing the regions supplied by the posterior, middle, and anterior [[cerebral arteries]].]]
Blood supply to the cerebral cortex is part of the [[cerebral circulation]]. [[Cerebral arteries]] supply the blood that [[Perfusion|perfuses]] the cerebrum. This arterial blood carries oxygen, glucose, and other nutrients to the cortex. [[Cerebral veins]] drain the deoxygenated blood, and metabolic wastes including carbon dioxide, back to the heart.

The main arteries supplying the cortex are the [[anterior cerebral artery]], the [[middle cerebral artery]], and the [[posterior cerebral artery]]. The anterior cerebral artery supplies the anterior portions of the brain, including most of the frontal lobe. The middle cerebral artery supplies the parietal lobes, temporal lobes, and parts of the occipital lobes. The middle cerebral artery splits into two branches to supply the left and right hemisphere, where they branch further. The posterior cerebral artery supplies the occipital lobes.

The [[circle of Willis]] is the main blood system that deals with blood supply in the cerebrum and cerebral cortex.
[[File:Cerebral vascular territories.jpg|thumb|left|Cortical blood supply]]
{{Clear}}

== Development ==
{{See also|Development of the cerebral cortex}}
The [[prenatal development]] of the cerebral cortex is a complex and finely tuned process called [[Development of the human cerebral cortex|corticogenesis]], influenced by the interplay between genes and the environment.<ref>{{cite journal | vauthors = Pletikos M, Sousa AM, Sedmak G, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N | title = Temporal specification and bilaterality of human neocortical topographic gene expression | journal = Neuron | volume = 81 | issue = 2 | pages = 321–332 | date = January 2014 | pmid = 24373884 | pmc = 3931000 | doi = 10.1016/j.neuron.2013.11.018 }}</ref>

===Neural tube===
The cerebral cortex develops from the most anterior part, the forebrain region, of the [[neural tube]].<ref name="Wolpert">{{cite book | vauthors = Wolpert L |title=Principles of Development |date=2015 |publisher=Oxford University Press |location=UK |isbn=978-0-19-967814-3 |page=533 |edition=Fifth}}</ref><ref name="pmid10498281">{{cite journal | vauthors = Warren N, Caric D, Pratt T, Clausen JA, Asavaritikrai P, Mason JO, Hill RE, Price DJ | title = The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex | journal = Cerebral Cortex | volume = 9 | issue = 6 | pages = 627–635 | date = September 1999 | pmid = 10498281 | doi = 10.1093/cercor/9.6.627 | doi-access = free }}</ref> The [[neural plate]] folds and closes to form the [[neural tube]]. From the cavity inside the neural tube develops the [[ventricular system]], and, from the [[neuroepithelial cell]]s of its walls, the [[neuron]]s and [[neuroglia|glia]] of the nervous system. The most anterior (front, or cranial) part of the neural plate, the [[prosencephalon]], which is evident before [[neurulation]] begins, gives rise to the cerebral hemispheres and later cortex.<ref>{{cite book | vauthors = Larsen WJ, Sherman LS, Potter SS, Scott WJ |title=Human Embryology |date=2001 |publisher=Churchill Livingstone |location=New York |isbn=978-0-443-06583-5 |edition=3rd | pages = 421–422 }}</ref>

===Cortical neuron development===
{{Further|Neurogenesis|Neuroepithelial cell}}
Cortical neurons are generated within the [[ventricular zone]], next to the [[ventricular system|ventricle]]s. At first, this zone contains [[neural stem cell]]s, that transition to [[radial glial cell]]s–progenitor cells, which divide to produce glial cells and neurons.<ref>{{cite journal | vauthors = Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR | title = Neurons derived from radial glial cells establish radial units in neocortex | journal = Nature | volume = 409 | issue = 6821 | pages = 714–720 | date = February 2001 | pmid = 11217860 | doi = 10.1038/35055553 | s2cid = 3041502 | bibcode = 2001Natur.409..714N | author3-link = Tamily Weissman }}</ref>

====Radial glia====
[[File:Neurogenesis and Differentiation of Cortical Layers.jpg|thumb|Neurogenesis is shown in red and lamination is shown in blue. Adapted from (Sur et al. 2001)]]
The cerebral cortex is composed of a heterogenous population of cells that give rise to different cell types. The majority of these cells are derived from [[Radial glial cell|radial glia]] migration that form the different cell types of the neocortex and it is a period associated with an increase in [[neurogenesis]]. Similarly, the process of neurogenesis regulates lamination to form the different layers of the cortex. During this process there is an increase in the restriction of cell fate that begins with earlier [[Progenitor cell|progenitors]] giving rise to any cell type in the cortex and later progenitors giving rise only to [[neuron]]s of superficial layers. This differential cell fate creates an inside-out topography in the cortex with younger neurons in superficial layers and older neurons in deeper layers. In addition, laminar neurons are stopped in [[Cell cycle|S]] or [[G2 phase]] in order to give a fine distinction between the different cortical layers. Laminar differentiation is not fully complete until after birth since during development laminar neurons are still sensitive to extrinsic signals and environmental cues.<ref>{{cite journal | vauthors = Sur M, Leamey CA | title = Development and plasticity of cortical areas and networks | journal = Nature Reviews. Neuroscience | volume = 2 | issue = 4 | pages = 251–262 | date = April 2001 | pmid = 11283748 | doi = 10.1038/35067562 | s2cid = 893478 }}</ref>

Although the majority of the cells that compose the cortex are derived locally from radial glia there is a subset population of neurons that [[cell migration|migrate]] from other regions. Radial glia give rise to neurons that are pyramidal in shape and use [[Glutamate (neurotransmitter)|glutamate]] as a [[neurotransmitter]], however these migrating cells contribute neurons that are stellate-shaped and use [[Gamma-Aminobutyric acid|GABA]] as their main neurotransmitter. These GABAergic neurons are generated by progenitor cells in the [[medial ganglionic eminence]] (MGE) that migrate tangentially to the cortex via the [[subventricular zone]]. This migration of GABAergic neurons is particularly important since [[GABA receptor]]s are excitatory during development. This excitation is primarily driven by the flux of chloride ions through the GABA receptor, however in adults chloride concentrations shift causing an inward flux of chloride that [[Hyperpolarization (biology)|hyperpolarizes]] [[postsynaptic neuron]]s.<ref name="Sanes_2012">{{Cite book |title=Development of the Nervous System | vauthors = Sanes DH, Reh TA, Harris WA |publisher=Elsevier Inc. |year=2012 |isbn=978-0-12-374539-2}}</ref>
The glial fibers produced in the first divisions of the progenitor cells are radially oriented, spanning the thickness of the cortex from the [[ventricular zone]] to the outer, [[Pia mater|pia]]l surface, and provide scaffolding for the migration of neurons outwards from the [[ventricular zone]].<ref>{{cite journal | vauthors = Rakic P | title = Evolution of the neocortex: a perspective from developmental biology | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 10 | pages = 724–735 | date = October 2009 | pmid = 19763105 | pmc = 2913577 | doi = 10.1038/nrn2719 }}</ref><ref>{{cite journal | vauthors = Rakic P | title = Extrinsic cytological determinants of basket and stellate cell dendritic pattern in the cerebellar molecular layer | journal = The Journal of Comparative Neurology | volume = 146 | issue = 3 | pages = 335–354 | date = November 1972 | pmid = 4628749 | doi = 10.1002/cne.901460304 | s2cid = 31900267 }}</ref>

At birth there are very few [[dendrite]]s present on the cortical neuron's cell body, and the axon is undeveloped. During the first year of life the dendrites become dramatically increased in number, such that they can accommodate up to a hundred thousand [[synapse|synaptic connections]] with other neurons. The axon can develop to extend a long way from the cell body.<ref name="Gilbert2">{{cite book | vauthors = Gilbert S |title=Developmental Biology |date=2006 |publisher=Sinauer Associates Publishers |isbn=978-0-87893-250-4 |pages=394–395 |edition=8th}}</ref>

===Asymmetric division===
The first divisions of the progenitor cells are symmetric, which duplicates the total number of progenitor cells at each [[Mitosis|mitotic cycle]]. Then, some progenitor cells begin to divide asymmetrically, producing one postmitotic cell that migrates along the radial glial fibers, leaving the [[ventricular zone]], and one progenitor cell, which continues to divide until the end of development, when it differentiates into a [[astrocyte|glial cell]] or an [[ependyma|ependymal cell]]. As the [[G1 phase]] of [[mitosis]] is elongated, in what is seen as selective cell-cycle lengthening, the newly born neurons migrate to more superficial layers of the cortex.<ref>{{cite journal | vauthors = Calegari F, Haubensak W, Haffner C, Huttner WB | title = Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development | journal = The Journal of Neuroscience | volume = 25 | issue = 28 | pages = 6533–6538 | date = July 2005 | pmid = 16014714 | pmc = 6725437 | doi = 10.1523/jneurosci.0778-05.2005 }}</ref> The migrating daughter cells become the [[pyramidal cell]]s of the cerebral cortex.<ref>{{cite journal | vauthors = Rakic P | title = Specification of cerebral cortical areas | journal = Science | volume = 241 | issue = 4862 | pages = 170–176 | date = July 1988 | pmid = 3291116 | doi = 10.1126/science.3291116 | bibcode = 1988Sci...241..170R }}</ref> The development process is time ordered and regulated by hundreds of genes and [[Epigenetic Regulation of Neurogenesis|epigenetic regulatory mechanisms]].<ref>{{cite journal | vauthors = Hu XL, Wang Y, Shen Q | title = Epigenetic control on cell fate choice in neural stem cells | journal = Protein & Cell | volume = 3 | issue = 4 | pages = 278–290 | date = April 2012 | pmid = 22549586 | pmc = 4729703 | doi = 10.1007/s13238-012-2916-6 }}</ref>

===Layer organization===
[[File:Human Cortical Development.png|right|thumb|Human cortical development between 26 and 39 week gestational age]]
The [[laminar organization|layered structure]] of the mature cerebral cortex is formed during development. The first pyramidal neurons generated migrate out of the [[ventricular zone]] and [[subventricular zone]], together with [[reelin]]-producing [[Cajal–Retzius cell|Cajal–Retzius neurons]], from the '''preplate'''. Next, a cohort of neurons migrating into the middle of the preplate divides this transient layer into the superficial '''marginal zone''', which will become layer I of the mature neocortex, and the [[subplate]],<ref>{{cite journal | vauthors = Kostovic I, Rakic P | title = Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain | journal = The Journal of Comparative Neurology | volume = 297 | issue = 3 | pages = 441–470 | date = July 1990 | pmid = 2398142 | doi = 10.1002/cne.902970309 | s2cid = 21371568 }}</ref> forming a middle layer called the '''cortical plate'''. These cells will form the deep layers of the mature cortex, layers five and six. Later born neurons migrate radially into the cortical plate past the deep layer neurons, and become the upper layers (two to four). Thus, the layers of the cortex are created in an inside-out order.<ref>{{cite journal | vauthors = Rakic P | title = Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition | journal = Science | volume = 183 | issue = 4123 | pages = 425–427 | date = February 1974 | pmid = 4203022 | doi = 10.1126/science.183.4123.425 | s2cid = 10881759 | bibcode = 1974Sci...183..425R }}</ref> The only exception to this inside-out sequence of [[neurogenesis]] occurs in the layer I of [[primate]]s, in which, in contrast to [[rodent]]s, neurogenesis continues throughout the entire period of [[corticogenesis]].<ref>{{cite journal | vauthors = Zecevic N, Rakic P | title = Development of layer I neurons in the primate cerebral cortex | journal = The Journal of Neuroscience | volume = 21 | issue = 15 | pages = 5607–5619 | date = August 2001 | pmid = 11466432 | pmc = 6762645 | doi = 10.1523/JNEUROSCI.21-15-05607.2001 }}</ref>

===Cortical patterning===
[[File:Emx2_and_Pax6_Expression.png|thumb|Depicted in blue, Emx2 is highly expressed at the caudomedial pole and dissipates outward. Pax6 expression is represented in purple and is highly expressed at the rostral lateral pole. (Adapted from Sanes, D., Reh, T., & Harris, W. (2012). ''Development of the Nervous System'' (3rd ed.). Burlington: Elsevier Science)]]
The map of functional cortical areas, which include primary motor and visual cortex, originates from a '[[Protomap (neuroscience)|protomap]]',<ref>{{cite journal | vauthors = Rakic P | title = Specification of cerebral cortical areas | journal = Science | volume = 241 | issue = 4862 | pages = 170–176 | date = July 1988 | pmid = 3291116 | doi = 10.1126/science.3291116 | bibcode = 1988Sci...241..170R }}</ref> which is regulated by molecular signals such as [[fibroblast growth factor]] [[FGF8]] early in embryonic development.<ref>{{cite journal | vauthors = Fukuchi-Shimogori T, Grove EA | title = Neocortex patterning by the secreted signaling molecule FGF8 | journal = Science | volume = 294 | issue = 5544 | pages = 1071–1074 | date = November 2001 | pmid = 11567107 | doi = 10.1126/science.1064252 | s2cid = 14807054 | doi-access = free | bibcode = 2001Sci...294.1071F }}</ref><ref>{{cite journal | vauthors = Garel S, Huffman KJ, Rubenstein JL | title = Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants | journal = Development | volume = 130 | issue = 9 | pages = 1903–1914 | date = May 2003 | pmid = 12642494 | doi = 10.1242/dev.00416 | s2cid = 6533589 | doi-access =  }}</ref> These signals regulate the size, shape, and position of cortical areas on the surface of the cortical primordium, in part by regulating gradients of [[transcription factor]] expression, through a process called [[cortical patterning]]. Examples of such transcription factors include the genes [[EMX2]] and [[PAX6]].<ref>{{cite journal | vauthors = Bishop KM, Goudreau G, O'Leary DD | title = Regulation of area identity in the mammalian neocortex by Emx2 and Pax6 | journal = Science | volume = 288 | issue = 5464 | pages = 344–349 | date = April 2000 | pmid = 10764649 | doi = 10.1126/science.288.5464.344 | bibcode = 2000Sci...288..344B }}</ref> Together, both [[transcription factor]]s form an opposing gradient of expression. [[PAX6|Pax6]] is highly expressed at the [[Anatomical terms of location|rostral lateral]] pole, while [[EMX2|Emx2]] is highly expressed in the [[Anatomical terms of location|caudomedial]] pole. The establishment of this gradient is important for proper development. For example, [[mutation]]s in Pax6 can cause expression levels of Emx2 to expand out of its normal expression domain, which would ultimately lead to an expansion of the areas normally derived from the caudal medial cortex, such as the [[visual cortex]]. On the contrary, if mutations in Emx2 occur, it can cause the Pax6-expressing domain to expand and result in the [[Frontal lobe|frontal]] and [[Motor cortex|motor cortical]] regions enlarging. Therefore, researchers believe that similar gradients and [[Cell signaling|signaling centers]] next to the cortex could contribute to the regional expression of these transcription factors.<ref name="Sanes_2012" />
Two very well studied patterning signals for the cortex include [[Fibroblast growth factor|FGF]] and [[retinoic acid]]. If FGFs are [[Protein production|misexpressed]] in different areas of the developing cortex, [[cortical patterning]] is disrupted. Specifically, when [[FGF8|Fgf8]] is increased in the [[Anatomical terms of location|anterior]] pole, Emx2 is [[Downregulation and upregulation|downregulated]] and a [[caudal (anatomical term)|caudal]] shift in the cortical region occurs. This ultimately causes an expansion of the rostral regions. Therefore, Fgf8 and other FGFs play a role in the regulation of expression of Emx2 and Pax6 and represent how the cerebral cortex can become specialized for different functions.<ref name="Sanes_2012" />

Rapid expansion of the cortical surface area is regulated by the amount of self-renewal of [[radial glial cell]]s and is partly regulated by [[Fibroblast growth factor|FGF]] and [[Notch signaling pathway|Notch genes]].<ref>{{cite journal | vauthors = Rash BG, Lim HD, Breunig JJ, Vaccarino FM | title = FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis | journal = The Journal of Neuroscience | volume = 31 | issue = 43 | pages = 15604–15617 | date = October 2011 | pmid = 22031906 | pmc = 3235689 | doi = 10.1523/jneurosci.4439-11.2011 }}</ref> During the period of cortical neurogenesis and layer formation, many higher mammals begin the process of [[gyrification]], which generates the characteristic folds of the cerebral cortex.<ref>{{cite journal | vauthors = Rajagopalan V, Scott J, Habas PA, Kim K, Corbett-Detig J, Rousseau F, Barkovich AJ, Glenn OA, Studholme C | title = Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero | journal = The Journal of Neuroscience | volume = 31 | issue = 8 | pages = 2878–2887 | date = February 2011 | pmid = 21414909 | pmc = 3093305 | doi = 10.1523/jneurosci.5458-10.2011 }}</ref><ref>{{cite journal | vauthors = Lui JH, Hansen DV, Kriegstein AR | title = Development and evolution of the human neocortex | journal = Cell | volume = 146 | issue = 1 | pages = 18–36 | date = July 2011 | pmid = 21729779 | pmc = 3610574 | doi = 10.1016/j.cell.2011.06.030 }}</ref> Gyrification is regulated by a DNA-associated protein [[Trnp1]]<ref>{{cite journal | vauthors = Stahl R, Walcher T, De Juan Romero C, Pilz GA, Cappello S, Irmler M, Sanz-Aquela JM, Beckers J, Blum R, Borrell V, Götz M | title = Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate | journal = Cell | volume = 153 | issue = 3 | pages = 535–549 | date = April 2013 | pmid = 23622239 | doi = 10.1016/j.cell.2013.03.027 | hdl-access = free | doi-access = free | hdl = 10261/338716 }}</ref> and by FGF and [[Sonic hedgehog|SHH]] signaling.<ref>{{cite journal | vauthors = Wang L, Hou S, Han YG | title = Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex | journal = Nature Neuroscience | volume = 19 | issue = 7 | pages = 888–896 | date = July 2016 | pmid = 27214567 | pmc = 4925239 | doi = 10.1038/nn.4307 }}</ref><ref>{{cite journal | vauthors = Rash BG, Tomasi S, Lim HD, Suh CY, Vaccarino FM | title = Cortical gyrification induced by fibroblast growth factor 2 in the mouse brain | journal = The Journal of Neuroscience | volume = 33 | issue = 26 | pages = 10802–10814 | date = June 2013 | pmid = 23804101 | pmc = 3693057 | doi = 10.1523/JNEUROSCI.3621-12.2013 }}</ref>

==Evolution==
{{See also|Pallium (neuroanatomy)#Evolution}}
Of all the different brain regions, the cerebral cortex shows the largest evolutionary variation and has evolved most recently.<ref name="ReferenceA"/> In contrast to the highly conserved circuitry of the [[medulla oblongata]], for example, which serves critical functions such as regulation of heart and respiration rates, many areas of the cerebral cortex are not strictly necessary for survival. Thus, the evolution of the cerebral cortex has seen the advent and modification of new functional areas—particularly association areas that do not directly receive input from outside the cortex.<ref name="ReferenceA"/>

A key theory of cortical evolution is embodied in the [[radial unit hypothesis]] and related [[Protomap (neuroscience)|protomap]] hypothesis, first proposed by Rakic.<ref>{{cite journal | vauthors = Rakic P | title = Specification of cerebral cortical areas | journal = Science | volume = 241 | issue = 4862 | pages = 170–176 | date = July 1988 | pmid = 3291116 | doi = 10.1126/science.3291116 | bibcode = 1988Sci...241..170R }}</ref> This theory states that new cortical areas are formed by the addition of new radial units, which is accomplished at the [[stem cell]] level. The protomap hypothesis states that the cellular and molecular identity and characteristics of neurons in each cortical area are specified by cortical [[stem cell]]s, known as [[radial glial cell]]s, in a primordial map. This map is controlled by secreted signaling [[protein]]s and downstream [[transcription factor]]s.<ref>{{cite journal | vauthors = Fukuchi-Shimogori T, Grove EA | title = Neocortex patterning by the secreted signaling molecule FGF8 | journal = Science | volume = 294 | issue = 5544 | pages = 1071–1074 | date = November 2001 | pmid = 11567107 | doi = 10.1126/science.1064252 | bibcode = 2001Sci...294.1071F | s2cid = 14807054 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bishop KM, Goudreau G, O'Leary DD | title = Regulation of area identity in the mammalian neocortex by Emx2 and Pax6 | journal = Science | volume = 288 | issue = 5464 | pages = 344–349 | date = April 2000 | pmid = 10764649 | doi = 10.1126/science.288.5464.344 | bibcode = 2000Sci...288..344B }}</ref><ref>{{cite journal | vauthors = Grove EA, Fukuchi-Shimogori T | title = Generating the cerebral cortical area map | journal = Annual Review of Neuroscience | volume = 26 | pages = 355–380 | date = 2003 | pmid = 14527269 | doi = 10.1146/annurev.neuro.26.041002.131137 | s2cid = 12282525 }}</ref>

== Function ==
[[File:Constudproc.png|thumb|Some functional areas of cortex]]

===Connections===
The cerebral cortex is connected to various subcortical structures such as the [[thalamus]] and the [[basal ganglia]], sending information to them along [[efferent nerve fiber|efferent connections]] and receiving information from them via [[afferent nerve fiber|afferent connections]]. Most sensory information is routed to the cerebral cortex via the thalamus. Olfactory information, however, passes through the [[olfactory bulb]] to the olfactory cortex ([[piriform cortex]]). The majority of connections are from one area of the cortex to another, rather than from subcortical areas; [[Valentino Braitenberg|Braitenberg]] and Schüz (1998) claim that in primary sensory areas, at the cortical level where the input fibers terminate, up to 20% of the synapses are supplied by extracortical afferents but that in other areas and other layers the percentage is likely to be much lower.<ref>{{cite book | vauthors = Braitenberg V, Schüz A | title = Cortex: Statistics and Geometry of Neuronal Connectivity. | location = New York | publisher = Springer Science & Business Media | date = 1998 | isbn = 978-3-540-63816-2 }}</ref>

===Cortical areas===
{{See also|Cortical map}}
The whole of the cerebral cortex was divided into 52 different areas in an early presentation by [[Korbinian Brodmann]]. These areas, known as [[Brodmann area]]s, are based on their [[cytoarchitecture]] but also relate to various functions. An example is Brodmann area 17, which is the [[Visual cortex#Primary visual cortex (V1)|primary visual cortex]].

In more general terms the cortex is typically described as comprising three parts: sensory, motor, and association areas.

====Sensory areas====
[[File:Blausen 0102 Brain Motor&Sensory.png|thumb|Motor and sensory regions of the cerebral cortex]]

The sensory areas are the cortical areas that receive and process information from the [[senses]]. Parts of the cortex that receive sensory inputs from the [[thalamus]] are called primary sensory areas. The senses of vision, hearing, and touch are served by the primary visual cortex, primary [[auditory cortex]] and [[primary somatosensory cortex]] respectively. In general, the two hemispheres receive information from the opposite (contralateral) side of the [[Human body|body]]. For example, the right primary somatosensory cortex receives information from the left limbs, and the right visual cortex receives information from the left visual [[receptive field|field]].

The organization of sensory maps in the cortex reflects that of the corresponding sensing organ, in what is known as a [[Topographic map (Neuroanatomy)|topographic map]]. Neighboring points in the primary [[visual cortex]], for example, correspond to neighboring points in the [[retina]]. This topographic map is called a [[retinotopy|retinotopic map]]. In the same way, there exists a [[tonotopy|tonotopic map]] in the primary auditory cortex and a [[somatotopy|somatotopic map]] in the primary sensory cortex. This last topographic map of the body onto the [[posterior central gyrus]] has been illustrated as a deformed human representation, the somatosensory [[Cortical homunculus|homunculus]], where the size of different body parts reflects the relative density of their innervation. Areas with much sensory innervation, such as the fingertips and the lips, require more cortical area to process finer sensation.

====Motor areas====
The motor areas are located in both hemispheres of the cortex. The motor areas are very closely related to the control of voluntary movements, especially fine fragmented movements performed by the hand. The right half of the motor area controls the left side of the body, and vice versa.

Two areas of the cortex are commonly referred to as motor:
* [[Primary motor cortex]], which ''executes'' voluntary movements <ref>{{Cite book | vauthors = Moini J, Piran P |chapter=Chapter 6 - Cerebral cortex |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780128174241000069 | veditors = Moini J, Piran P |title= Functional and Clinical Neuroanatomy: A Guide for Health Care Professionals |date=January 2020 |pages=177–240 |publisher=Academic Press |doi=10.1016/B978-0-12-817424-1.00006-9 |isbn=978-0-12-817424-1 }}</ref>
* [[Supplementary motor area]]s and [[premotor cortex]], which ''select'' voluntary movements.<ref>{{Cite book | vauthors = Michelet T, Burbaud P, Gross CE, Bioulac B | chapter = Behavioral Planning: Neurophysiological Approach of the Frontal Lobe Function in Primates |chapter-url= https://www.sciencedirect.com/science/article/abs/pii/B978008045396500213X | veditors = Koob GF, Le Moal M, Thompson RF |title= Encyclopedia of Behavioral Neuroscience|date=January 2010 |pages=145–152 |publisher=Academic Press |doi=10.1016/B978-0-08-045396-5.00213-X |isbn=978-0-08-045396-5 }}</ref>

In addition, motor functions have been described for:
* [[Posterior parietal cortex]], which guides voluntary movements in space
* [[Dorsolateral prefrontal cortex]], which decides which voluntary movements to make according to higher-order instructions, rules, and self-generated thoughts.

Just underneath the cerebral cortex are interconnected subcortical masses of grey matter called [[basal ganglia]] (or nuclei). The basal ganglia receive input from the substantia nigra of the midbrain and motor areas of the cerebral cortex, and send signals back to both of these locations. They are involved in motor control. They are found lateral to the thalamus. The main components of the basal ganglia are the [[caudate nucleus]], the [[putamen]], the [[globus pallidus]], the [[substantia nigra]], the [[nucleus accumbens]], and the [[subthalamic nucleus]]. The putamen and globus pallidus are also collectively known as the [[lentiform nucleus]], because together they form a lens-shaped body. The putamen and caudate nucleus are also collectively called the [[corpus striatum]] after their striped appearance.<ref>Saladin, Kenneth. Anatomy and Physiology: The Unity of Form and Function, 5th Ed. New York: McGraw-Hill Companies Inc., 2010. Print.</ref><ref>Dorland's Medical Dictionary for Health Consumers, 2008.</ref>

====Association areas====
[[File:Cortical areas that have been shown to be involved in speech processing fnhum-06-00099-g005.jpg|thumb|Cortical areas involved in speech processing.]]
The association areas are the parts of the cerebral cortex that do not belong to the primary regions. They function to produce a meaningful [[perception|perceptual experience]] of the world, enable us to interact effectively, and support abstract thinking and language. The [[parietal lobe|parietal]], [[Temporal lobe|temporal]], and [[occipital lobe]]s – all located in the posterior part of the cortex – integrate sensory information and information stored in memory. The [[frontal lobe]] or prefrontal association complex is involved in planning actions and movement, as well as abstract thought. Globally, the association areas are organized as distributed networks.<ref>{{cite journal | vauthors = Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zöllei L, Polimeni JR, Fischl B, Liu H, Buckner RL | title = The organization of the human cerebral cortex estimated by intrinsic functional connectivity | journal = Journal of Neurophysiology | volume = 106 | issue = 3 | pages = 1125–1165 | date = September 2011 | pmid = 21653723 | pmc = 3174820 | doi = 10.1152/jn.00338.2011 }}</ref> Each network connects areas distributed across widely spaced regions of the cortex. Distinct networks are positioned adjacent to one another yielding a complex series of interwoven networks. The specific organization of the association networks is debated with evidence for interactions, hierarchical relationships, and competition between networks.

In humans, association networks are particularly important to language function. In the past it was theorized that language abilities are localized in [[Broca's area]] in areas of the left [[inferior frontal gyrus]], [[Brodmann area 44|BA44]] and [[Brodmann area 45|BA45]], for language expression and in [[Wernicke's area]] [[Brodmann area|BA22]], for language reception. However, the processes of language expression and reception have been shown to occur in areas other than just those structures around the [[lateral sulcus]], including the frontal lobe, [[basal ganglia]], [[cerebellum]], and [[pons]].<ref>{{cite journal | vauthors = Price CJ | title = The anatomy of language: contributions from functional neuroimaging | journal = Journal of Anatomy | volume = 197 Pt 3 | issue = Pt 3 | pages = 335–359 | date = October 2000 | pmid = 11117622 | pmc = 1468137 | doi = 10.1046/j.1469-7580.2000.19730335.x }}</ref>

==Clinical significance==
{{Further|Central nervous system disease|Developmental toxicity}}
[[File:Middle Cerebral Artery occlusion. Kentar et al Acta Neuroch 2020.gif|thumb|507x507px|Hemodynamic changes observed on gyrencephalic brain cortex after an arterial vessel occlusion in IOS. The video has a speed of 50x to better appreciate the [[Cortical spreading depression|spreading depolarization]] over the brain cortex. Pictures are dynamically subtracted to a reference picture 40 s before. First we see the initial area of change at the exact moment where the middle cerebral artery group (left) is occluded. The area is highlighted with a white line. Later we appreciate the signal produced by Spreading Depolarizations. We see markedly the front of waves.<ref>{{cite journal | vauthors = Kentar M, Mann M, Sahm F, Olivares-Rivera A, Sanchez-Porras R, Zerelles R, Sakowitz OW, Unterberg AW, Santos E | title = Detection of spreading depolarizations in a middle cerebral artery occlusion model in swine | journal = Acta Neurochirurgica | volume = 162 | issue = 3 | pages = 581–592 | date = March 2020 | pmid = 31940093 | doi = 10.1007/s00701-019-04132-8 | s2cid = 210196036 }}</ref> <nowiki>https://doi.org/10.1007/s00701-019-04132-8</nowiki>]]
[[Neurodegenerative disease]]s such as [[Alzheimer's disease]], show as a marker, an atrophy of the grey matter of the cerebral cortex.<ref name="Nakazawa">{{cite journal | vauthors = Nakazawa T, Ohara T, Hirabayashi N, Furuta Y, Hata J, Shibata M, Honda T, Kitazono T, Nakao T, Ninomiya T | title = Multiple-region grey matter atrophy as a predictor for the development of dementia in a community: the Hisayama Study | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 93 | issue = 3 | pages = 263–271 | date = March 2022 | pmid = 34670843 | pmc = 8862082 | doi = 10.1136/jnnp-2021-326611 }}</ref>

Other [[Central nervous system disease|diseases of the central nervous system]] include [[neurological disorder]]s such as [[epilepsy]], [[movement disorder]]s, and [[Aphasia#Boston classification|different types of aphasia]] (difficulties in speech expression or comprehension).

[[Brain damage]] from disease or trauma, can involve damage to a specific lobe such as in [[frontal lobe disorder]], and associated functions will be affected. The [[blood–brain barrier]] that serves to protect the brain from infection can become compromised allowing entry to [[pathogen]]s.

The [[prenatal development|developing fetus]] is susceptible to a range of environmental factors that can cause [[birth defect]]s and problems in later development. Maternal alcohol consumption for example can cause [[fetal alcohol spectrum disorder]].<ref name="Mukherjee_2006">{{cite journal | vauthors = Mukherjee RA, Hollins S, Turk J | title = Fetal alcohol spectrum disorder: an overview | journal = Journal of the Royal Society of Medicine | volume = 99 | issue = 6 | pages = 298–302 | date = June 2006 | pmid = 16738372 | pmc = 1472723 | doi = 10.1177/014107680609900616 }}</ref> Other factors that can cause neurodevelopment disorders are [[Environmental toxicants and fetal development|toxicants]] such as [[drug]]s, and exposure to [[radiation]] as from [[X-ray]]s. Infections can also affect the development of the cortex. A viral infection is one of the causes of [[lissencephaly]], which results in a smooth cortex without [[gyrification]].

A type of [[electrocorticography]] called [[cortical stimulation mapping]] is an invasive procedure that involves placing [[electrode]]s directly onto the exposed brain in order to localise the functions of specific areas of the cortex. It is used in clinical and therapeutic applications including pre-surgical mapping.<ref name="Tarapore">{{cite journal | vauthors = Tarapore PE, Tate MC, Findlay AM, Honma SM, Mizuiri D, Berger MS, Nagarajan SS | title = Preoperative multimodal motor mapping: a comparison of magnetoencephalography imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation | journal = Journal of Neurosurgery | volume = 117 | issue = 2 | pages = 354–362 | date = August 2012 | pmid = 22702484 | pmc = 4060619 | doi = 10.3171/2012.5.JNS112124 }}</ref>

===Genes associated with cortical disorders===
There are a number of genetic mutations that can cause a wide range of [[genetic disorder]]s of the cerebral cortex, including [[microcephaly]], [[schizencephaly]] and types of [[lissencephaly]].<ref name="Walsh">{{cite journal | vauthors = Mochida GH, Walsh CA | title = Genetic basis of developmental malformations of the cerebral cortex | journal = Archives of Neurology | volume = 61 | issue = 5 | pages = 637–640 | date = May 2004 | pmid = 15148137 | doi = 10.1001/archneur.61.5.637 | doi-access =  }}</ref> [[Chromosome abnormality|Chromosome abnormalities]] can also result causing a number of [[neurodevelopmental disorder]]s such as [[fragile X syndrome]] and [[Rett syndrome]].

[[MCPH1]] codes for [[microcephalin]], and disorders in this and in [[ASPM (gene)|ASPM]] are associated with microcephaly.<ref name="Walsh"/> Mutations in the gene [[NBS1]] that codes for [[nibrin]] can cause [[Nijmegen breakage syndrome]], characterised by microcephaly.<ref name="Walsh"/>

Mutations in [[EMX2]],<ref name="nih">{{cite web |title=EMX2 empty spiracles homeobox 2 [Homo sapiens (human)] | work = Gene – NCBI |url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2018 | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine }}</ref> and [[COL4A1]] are associated with [[schizencephaly]],<ref name="Smigiel">{{cite journal | vauthors = Smigiel R, Cabala M, Jakubiak A, Kodera H, Sasiadek MJ, Matsumoto N, Sasiadek MM, Saitsu H | title = Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection | journal = Birth Defects Research. Part A, Clinical and Molecular Teratology | volume = 106 | issue = 4 | pages = 304–307 | date = April 2016 | pmid = 26879631 | doi = 10.1002/bdra.23488 }}</ref> a condition marked by the absence of large parts of the cerebral hemispheres.

==History==
In 1909, [[Korbinian Brodmann]] distinguished 52 different regions of the cerebral cortex based on their cytoarchitecture. These are known as [[Brodmann area]]s.<ref name="McGraw-Hill Medical_2013">{{cite book |title=Principles of Neural Science |date=2013 |publisher=McGraw-Hill Medical |location=New York |isbn=978-0-07-139011-8 |edition=5th |pages=347–348 |oclc=795553723 |editor-last1=Kendel |editor-first1=Eric R. |editor-last2=Mack |editor-first2=Sarah}}</ref>

[[Rafael Lorente de Nó]], a student of [[Santiago Ramon y Cajal]], identified more than 40 different types of cortical neurons based on the distribution of their dendrites and axons.<ref name="McGraw-Hill Medical_2013" />

==Other animals==
{{See also|Barrel cortex}}
The cerebral cortex is derived from the [[pallium (neuroanatomy)|pallium]], a layered structure found in the [[prosencephalon|forebrain]] of all [[vertebrate]]s. The basic form of the pallium is a cylindrical layer enclosing fluid-filled ventricles. Around the circumference of the cylinder are four zones, the dorsal pallium, medial pallium, ventral pallium, and lateral pallium, which are thought to be [[Homology (biology)|homologous]] to the [[neocortex]], [[hippocampus]], [[amygdala]], and [[piriform cortex|olfactory cortex]], respectively.

In [[Avian brain|avian brains]], evidence suggests the [[avian pallium]]'s neuroarchitecture to be reminiscent of the mammalian cerebral cortex.<ref>{{cite journal | vauthors = Stacho M, Herold C, Rook N, Wagner H, Axer M, Amunts K, Güntürkün O | title = A cortex-like canonical circuit in the avian forebrain | journal = Science | volume = 369 | issue = 6511 | date = September 2020 | pmid = 32973004 | doi = 10.1126/science.abc5534 }}</ref> The avian pallium has also been suggested to be an equivalent neural basis for [[Animal consciousness|consciousness]].<ref>{{cite journal | vauthors = Nieder A, Wagener L, Rinnert P | title = A neural correlate of sensory consciousness in a corvid bird | journal = Science | volume = 369 | issue = 6511 | pages = 1626–1629 | date = September 2020 | pmid = 32973028 | doi = 10.1126/science.abb1447 | bibcode = 2020Sci...369.1626N | s2cid = 221881862 }}</ref><ref>{{cite journal | vauthors = Herculano-Houzel S | title = Birds do have a brain cortex-and think | journal = Science | volume = 369 | issue = 6511 | pages = 1567–1568 | date = September 2020 | pmid = 32973020 | doi = 10.1126/science.abe0536 | bibcode = 2020Sci...369.1567H | s2cid = 221882004 }}</ref>

Until recently no counterpart to the cerebral cortex had been recognized in invertebrates. However, a study published in the journal ''Cell'' in 2010, based on gene expression profiles, reported strong affinities between the cerebral cortex and the [[mushroom bodies]] of the [[Nereididae|ragworm]] ''[[Platynereis dumerilii]]''.<ref>{{cite journal | vauthors = Tomer R, Denes AS, Tessmar-Raible K, Arendt D | title = Profiling by image registration reveals common origin of annelid mushroom bodies and vertebrate pallium | journal = Cell | volume = 142 | issue = 5 | pages = 800–809 | date = September 2010 | pmid = 20813265 | doi = 10.1016/j.cell.2010.07.043 | s2cid = 917306 | doi-access = free }}</ref> Mushroom bodies are structures in the brains of many types of worms and arthropods that are known to play important roles in learning and memory; the genetic evidence indicates a common evolutionary origin, and therefore indicates that the origins of the earliest precursors of the cerebral cortex date back to the [[Precambrian]] era.

==Additional images==
<gallery>

File:Lateral surface of cerebral cortex - gyri.png|Lateral surface of the human cerebral cortex
File:Medial surface of cerebral cortex - entorhinal cortex.png|Medial surface of the human cerebral cortex
Brainmaps-macaque-hippocampus.jpg|Tissue slice from the brain of an adult [[macaque]] monkey. The cerebral cortex is depicted in dark violet. 

</gallery>

== See also ==
{{col div|colwidth=30em}}

* [[Brain–computer interface]]
* [[Cortical dysplasia]]
* [[Cortical homunculus]]
* [[Eloquent cortex]]
* [[EMX1]]
* [[Gray matter heterotopia]]
* [[Limbic system]]
* [[List of regions in the human brain]]
* [[Insular cortex]]

{{colend}}

== References ==
{{Reflist|2}}

== External links ==
* {{BrainInfo|hier|20}}
* {{BrainMaps|cerebral%20cortex|cerebral cortex}}
* [https://web.archive.org/web/20041229070957/http://webvision.med.utah.edu/VisualCortex.html "The primary visual cortex"], Webvision: Comprehensive article about the structure and function of the primary visual cortex.
* [https://web.archive.org/web/20160722010322/http://webvision.med.utah.edu/imageswv/BasicCells.jpg "Basic cell types"], Webvision: Image of the basic cell types of the monkey cerebral cortex.
* [https://web.archive.org/web/20161117212320/http://ccdb.ucsd.edu/sand/main?stype=lite&keyword=cerebral%20cortex&Submit=Go&event=display&start=1 Cerebral Cortex – Cell Centered Database]

{{Prosencephalon}}
{{Cortex types}}
{{Authority control}}

{{DEFAULTSORT:Cerebral Cortex}}
[[Category:Cerebral cortex| ]]