Editing Cerebral cortex (section)

== 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.