The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of

allocortex The allocortex or heterogenetic cortex, and neocortex are the two types of cerebral cortex in the brain. The allocortex is the much smaller area of cortex taking up just 10 %, the neocortex takes up the remaining 90 %. It is characterized by havi ...

. It is separated into two cortices, by the

longitudinal fissure The longitudinal fissure (or cerebral fissure, great longitudinal fissure, median longitudinal fissure, interhemispheric fissure) is the deep groove that separates the two cerebral hemispheres of the vertebrate brain. Lying within it is a continu ...

that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the

corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental m ...

. The cerebral cortex is the largest site of neural integration in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness. The cerebral cortex is part of the brain responsible for cognition. 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 cranium. Apart from minimising brain and cranial volume, cortical folding is crucial for the brain circuitry and its functional organisation. In mammals with small brains there is no folding and the cortex is smooth. A fold or ridge in the cortex is termed a

gyrus In neuroanatomy, a gyrus (pl. gyri) is a ridge on the cerebral cortex. It is generally surrounded by one or more sulci (depressions or furrows; sg. ''sulcus''). Gyri and sulci create the folded appearance of the brain in humans and other ...

(plural gyri) and a groove is termed a sulcus (plural sulci). These surface convolutions appear during

fetal development Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...

and continue to mature after birth through the process of

gyrification Gyrification is the process of forming the characteristic folds of the cerebral cortex. The peak of such a fold is called a ''gyrus'' (pl. ''gyri''), and its trough is called a '' sulcus'' (pl. ''sulci''). The neurons of the cerebral cortex re ...

. In the

human brain The human brain is the central organ (anatomy), organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the act ...

the majority of the cerebral cortex is not visible from the outside, but buried in the sulci. The major sulci and gyri mark the divisions of the cerebrum into the

lobes of the brain The lobes of the brain are the major identifiable zones of the cerebral cortex, and they comprise the surface of each hemisphere of the cerebrum. The two hemispheres are roughly symmetrical in structure, and are connected by the corpus callosum. ...

. The four major lobes are the frontal, parietal,

occipital The occipital bone () is a cranial dermal bone and the main bone of the occiput (back and lower part of the skull). It is trapezoidal in shape and curved on itself like a shallow dish. The occipital bone overlies the occipital lobes of the cereb ...

and temporal lobes. Other lobes are the limbic lobe, and the

insular cortex The insular cortex (also insula and insular lobe) is a portion of the cerebral cortex folded deep within the lateral sulcus (the fissure separating the temporal lobe from the parietal and frontal lobes) within each hemisphere of the mammalian b ...

often referred to as the ''insular lobe''. There are between 14 and 16 billion neurons in the human cerebral cortex. These are organised into horizontal cortical layers, and radially into cortical columns and minicolumns. Cortical areas have specific functions such as movement in the

motor cortex The motor cortex is the region of the cerebral cortex believed to be involved in the planning, control, and execution of voluntary movements. The motor cortex is an area of the frontal lobe located in the posterior precentral gyrus immediately ...

, and sight in the visual cortex. Visual cortex is located in the occipital lobe.

Structure

The cerebral cortex is the outer covering of the surfaces of the cerebral hemispheres and is folded into peaks called gyri, and grooves called

sulci Sulci or Sulki (in Greek , Steph. B., Ptol.; , Strabo; , Paus.), was one of the most considerable cities of ancient Sardinia, situated in the southwest corner of the island, on a small island, now called Isola di Sant'Antioco, which is, how ...

. In the

it is between two and three or four millimetres thick, and makes up 40 per cent of the brain's mass. 90 per cent of the cerebral cortex is the six-layered neocortex with the other 10 per cent made up of

. There are between 14 and 16 billion neurons in the cortex, and these are organized radially in cortical columns, and minicolumns, in the horizontally organized layers of the cortex. The neocortex is separable into different regions of cortex known in the plural as cortices, and include the

and visual cortex. About two thirds of the cortical surface is buried in the sulci and the

is completely hidden. The cortex is thickest over the top of a gyrus and thinnest at the bottom of a sulcus.

Folds

The cerebral cortex is folded in a way that allows a large surface area of neural tissue to fit within the confines of the

neurocranium In human anatomy, the neurocranium, also known as the braincase, brainpan, or brain-pan is the upper and back part of the skull, which forms a protective case around the brain. In the human skull, the neurocranium includes the calvaria or skul ...

. When unfolded in the human, each hemispheric cortex has a total surface area of about . The folding is inward away from the surface of the brain, and is also present on the medial surface of each hemisphere within the

. 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 rodents have smooth cerebral surfaces without

Lobes

The larger sulci and gyri mark the divisions of the cortex of the cerebrum into the

. There are four main lobes: the

frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove be ...

parietal lobe The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus. The parietal lobe integrates sensory informa ...

, temporal lobe, and

occipital lobe The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head". The occipital lobe is the vi ...

. The

is often included as the insular lobe. The limbic lobe is a rim of cortex on the medial side of each hemisphere and is also often included. There are also three lobules of the brain described: the paracentral lobule, the

superior parietal lobule The superior parietal lobule is bounded in front by the upper part of the postcentral sulcus, but is usually connected with the postcentral gyrus above the end of the sulcus. The superior parietal lobule contains Brodmann's areas 5 and 7. Beh ...

, and the

inferior parietal lobule The inferior parietal lobule (subparietal district) lies below the horizontal portion of the intraparietal sulcus, and behind the lower part of the postcentral sulcus. Also known as Geschwind's territory after Norman Geschwind, an American neur ...

Thickness

For species of mammals, larger brains (in absolute terms, not just in relation to body size) tend to have thicker cortices. The smallest mammals, such as shrews, have a neocortical thickness of about 0.5 mm; the ones with the largest brains, such as humans and fin whales, have thicknesses of 2–4 mm. There is an approximately logarithmic relationship between brain weight and cortical thickness.

Magnetic resonance imaging of the brain Magnetic resonance imaging of the brain uses magnetic resonance imaging (MRI) to produce high quality two-dimensional or three-dimensional images of the brain and brainstem as well as the cerebellum without the use of ionizing radiation (X-rays) or ...

(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. One study has found some positive association between the cortical thickness and

intelligence Intelligence has been defined in many ways: the capacity for abstraction, logic, understanding, self-awareness, learning, emotional knowledge, reasoning, planning, creativity, critical thinking, and problem-solving. More generally, it can be des ...

. Another study has found that the

somatosensory cortex In physiology, the somatosensory system is the network of neural structures in the brain and body that produce the perception of touch ( haptic perception), as well as temperature (thermoception), body position (proprioception), and pain. It i ...

is thicker in migraine patients, though it is not known if this is the result of migraine attacks or the cause of them. A later study using a larger patient population reports no change in the cortical thickness in patients with migraine. 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.

Layers of neocortex

The neocortex is formed of six layers, numbered I to VI, from the outermost layer I – near to the

pia mater Pia mater ( or ),Entry "pia mater"
in
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 cortical layering is the line of Gennari in the

primary visual cortex The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and ...

. This is a band of whiter tissue that can be observed with the naked eye in the

calcarine sulcus The calcarine sulcus (or calcarine fissure) is an anatomical landmark located at the caudal end of the medial surface of the brain of humans and other primates. Its name comes from the Latin "calcar" meaning "spur". It is very deep, and known ...

of the occipital lobe. The line of Gennari is composed of

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

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 Korbinian Brodmann (17 November 1868 – 22 August 1918) was a German neurologist who became famous for mapping the cerebral cortex and defining 52 distinct regions, known as Brodmann areas, based on their cytoarchitectonic (histological) char ...

(1909) established that the mammalian neocortex is consistently divided into six layers.

Layer I

Layer I is the molecular layer, and contains few scattered neurons, including GABAergic rosehip neurons. Layer I consists largely of extensions of apical dendritic tufts of pyramidal neurons and horizontally oriented axons, as well as

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

. During development, Cajal-Retzius cells and subpial granular layer cells 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. While it was once thought that the input to layer I came from the cortex itself, it is now realized that layer I across the cerebral cortex mantle receives substantial input from ''matrix'' or M-type thalamus cells (in contrast to ''core'' or C-type that go to layer IV).

Layer II

Layer II, the external granular layer, contains small 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 interhemispheric corticocortical afferents, and layer III is the principal source of corticocortical efferents.

Layer IV

Layer IV, the internal granular layer, contains different types of stellate and pyramidal cells, and is the main target of thalamocortical afferents from thalamus type C neurons (core-type) 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).

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 Betz cells (also known as pyramidal cells of Betz) are giant pyramidal cells (neurons) located within the fifth layer of the grey matter in the primary motor cortex. These neurons are the largest in the central nervous system, sometimes reaching ...

s, whose axons travel through the

internal capsule The internal capsule is a white matter structure situated in the inferomedial part of each cerebral hemisphere of the brain. It carries information past the basal ganglia, separating the caudate nucleus and the thalamus from the putamen and the ...

, the

brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...

, and the spinal cord forming the corticospinal tract, which is the main pathway for voluntary motor control.

Layer VI

Layer VI, the polymorphic or multiform layer, contains few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons; layer VI sends efferent fibers to the thalamus, establishing a very precise reciprocal interconnection between the cortex and the thalamus. 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 In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...

fibers to neurons in the thalamus and also send collaterals to the

thalamic reticular nucleus The thalamic reticular nucleus is part of the ventral thalamus that forms a capsule around the thalamus laterally. However, recent evidence from mice and fish question this statement and define it as a dorsal thalamic structure. It is separated fro ...

that

inhibit Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotr ...

these same thalamus neurons or ones adjacent to them. One theory is that because the inhibitory output is reduced by

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cati ...

input to the cerebral cortex, this provides the brainstem with adjustable "gain control for the relay of lemniscal inputs".

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 columns and minicolumns. It has been proposed that the minicolumns are the basic functional units of the cortex. In 1957,

Vernon Mountcastle Vernon Benjamin Mountcastle (July 15, 1918 – January 11, 2015) was an American neurophysiologist and Professor Emeritus of Neuroscience at Johns Hopkins University. He discovered and characterized the columnar organization of the cerebral co ...

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 Wiesel, 1959), auditory cortex, and associative cortex. Cortical areas that lack a layer IV are called agranular. Cortical areas that have only a rudimentary layer IV are called dysgranular. Information processing within each layer is determined by different temporal dynamics with that in layers II/III having a slow 2 Hz oscillation while that in layer V has a fast 10–15 Hz oscillation.

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

that has three or four layers: * 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

. 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 In anatomy of animals, the paleocortex, or paleopallium, is a region within the telencephalon in the vertebrate brain. This type of cortical tissue consists of three cortical laminae (layers of neuronal cell bodies). In comparison, the neocortex ...

with three cortical laminae, the archicortex which has four or five, and a transitional area adjacent to the allocortex, the

periallocortex Periallocortex is one of three subtypes of allocortex, the other two subtypes being paleocortex and archicortex. The periallocortex is formed at transition areas where any of the other two subtypes of allocortex borders with the neocortex (which ...

. 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 The paralimbic cortex is an area of three-layered Cerebral cortex, cortex that includes the following regions: the piriform cortex, entorhinal cortex, the parahippocampal cortex on the Anatomical terms of location#Left and right (lateral), and med ...

, 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: the

, temporal lobe, the

, and the

, named from their overlying bones of the skull.

Blood supply and drainage

Blood supply to the cerebral cortex is part of the

cerebral circulation Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Art ...

. Cerebral arteries supply the blood that 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 The middle cerebral artery (MCA) is one of the three major paired cerebral arteries that supply blood to the cerebrum. The MCA arises from the internal carotid artery and continues into the lateral sulcus where it then branches and projects to ma ...

, 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. Cerebral vascular territories

Development

The prenatal development of the cerebral cortex is a complex and finely tuned process called corticogenesis, influenced by the interplay between genes and the environment.

Neural tube

The cerebral cortex develops from the most anterior part, the forebrain region, of the

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, ...

. The

neural plate The neural plate is a key developmental structure that serves as the basis for the nervous system. Cranial to the primitive node of the embryonic primitive streak, ectodermal tissue thickens and flattens to become the neural plate. The region ant ...

folds and closes to form the

. From the cavity inside the neural tube develops the ventricular system, and, from the

neuroepithelial cell Neuroepithelial cells, or neuroectodermal cells, form the wall of the closed neural tube in early embryonic development. The neuroepithelial cells span the thickness of the tube's wall, connecting with the pial surface and with the ventricular or ...

s of its walls, the neurons and

glia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

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.

Cortical neuron development

Cortical neurons are generated within the

ventricular zone In vertebrates, the ventricular zone (VZ) is a transient embryonic layer of tissue containing neural stem cells, principally radial glial cells, of the central nervous system (CNS). The VZ is so named because it lines the ventricular system, whi ...

, next to the ventricles. At first, this zone contains

neural stem cell Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor ste ...

s, that transition to

radial glial cell Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and ...

s–progenitor cells, which divide to produce glial cells and neurons.

Radial glia

Neurogenesis and Differentiation of Cortical Layers

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 glia Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and ol ...

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 progenitors giving rise to any cell type in the cortex and later progenitors giving rise only to neurons 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 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. Although the majority of the cells that compose the cortex are derived locally from radial glia there is a subset population of neurons that migrate from other regions. Radial glia give rise to neurons that are pyramidal in shape and use glutamate as a neurotransmitter, however these migrating cells contribute neurons that are stellate-shaped and use 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 The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone ...

. This migration of GABAergic neurons is particularly important since GABA receptors 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 hyperpolarizes

postsynaptic neuron Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

s. The glial fibers produced in the first divisions of the progenitor cells are radially oriented, spanning the thickness of the cortex from the

to the outer, pial surface, and provide scaffolding for the migration of neurons outwards from the

. At birth there are very few dendrites 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 synaptic connections with other neurons. The axon can develop to extend a long way from the cell body.

Asymmetric division

The first divisions of the progenitor cells are symmetric, which duplicates the total number of progenitor cells at each mitotic cycle. Then, some progenitor cells begin to divide asymmetrically, producing one postmitotic cell that migrates along the radial glial fibers, leaving the

, and one progenitor cell, which continues to divide until the end of development, when it differentiates into a

glial cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

or an

ependymal cell The ependyma is the thin neuroepithelial ( simple columnar ciliated epithelium) lining of the ventricular system of the brain and the central canal of the spinal cord. The ependyma is one of the four types of neuroglia in the central nervous syst ...

. 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. The migrating daughter cells become the pyramidal cells of the cerebral cortex. The development process is time ordered and regulated by hundreds of genes and epigenetic regulatory mechanisms.

Layer organization

The layered structure of the mature cerebral cortex is formed during development. The first pyramidal neurons generated migrate out of the

and

, together with reelin-producing 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 The subplate, also called the subplate zone, together with the marginal zone and the cortical plate, in the fetus represents the developmental anlage of the mammalian cerebral cortex. It was first described, as a separate transient fetal zone ...

, 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. The only exception to this inside-out sequence of neurogenesis occurs in the layer I of primates, in which, in contrast to rodents, neurogenesis continues throughout the entire period of corticogenesis.

Cortical patterning

The map of functional cortical areas, which include primary motor and visual cortex, originates from a ' protomap', which is regulated by molecular signals such as

fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...

FGF8 Fibroblast growth factor 8 (FGF-8) is a protein that in humans is encoded by the ''FGF8'' gene. Function The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic an ...

early in embryonic development. 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. Together, both transcription factors form an opposing gradient of expression. Pax6 is highly expressed at the rostral lateral pole, while Emx2 is highly expressed in the caudomedial pole. The establishment of this gradient is important for proper development. For example, mutations 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 and motor cortical regions enlarging. Therefore, researchers believe that similar gradients and signaling centers next to the cortex could contribute to the regional expression of these transcription factors. Two very well studied patterning signals for the cortex include FGF and

retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in ...

. If FGFs are misexpressed in different areas of the developing cortex, cortical patterning is disrupted. Specifically, when

Fgf8 Fibroblast growth factor 8 (FGF-8) is a protein that in humans is encoded by the ''FGF8'' gene. Function The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic an ...

is increased in the anterior pole, Emx2 is

downregulated In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proc ...

and a 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. Rapid expansion of the cortical surface area is regulated by the amount of self-renewal of

s and is partly regulated by FGF and Notch genes. During the period of cortical neurogenesis and layer formation, many higher mammals begin the process of

, which generates the characteristic folds of the cerebral cortex. Gyrification is regulated by a DNA-associated protein Trnp1 and by FGF and SHH signaling

Evolution

Of all the different brain regions, the cerebral cortex shows the largest evolutionary variation and has evolved most recently. 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. A key theory of cortical evolution is embodied in the radial unit hypothesis and related protomap hypothesis, first proposed by Rakic. 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 cells, known as

s, in a primordial map. This map is controlled by secreted signaling

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s and downstream transcription factors.

Function

Connections

The cerebral cortex is connected to various subcortical structures such as the thalamus and the basal ganglia, sending information to them along efferent connections and receiving information from them via 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 piriform cortex, or pyriform cortex, is a region in the brain, part of the rhinencephalon situated in the cerebrum. The function of the piriform cortex relates to the sense of smell. Structure The piriform cortex is part of the rhinencepha ...

). The majority of connections are from one area of the cortex to another, rather than from subcortical areas; 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.

Cortical areas

The whole of the cerebral cortex was divided into 52 different areas in an early presentation by

. These areas known as

Brodmann area A Brodmann area is a region of the cerebral cortex, in the human or other primate brain, defined by its cytoarchitecture, or histological structure and organization of cells. History Brodmann areas were originally defined and numbered by th ...

s, are based on their

cytoarchitecture Cytoarchitecture ( Greek '' κύτος''= "cell" + '' ἀρχιτεκτονική''= "architecture"), also known as cytoarchitectonics, is the study of the cellular composition of the central nervous system's tissues under the microscope. Cytoarc ...

but also relate to various functions. An example is Brodmann area 17 which is the

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

Sensory areas

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 The auditory cortex is the part of the temporal lobe that processes auditory information in humans and many other vertebrates. It is a part of the auditory system, performing basic and higher functions in hearing, such as possible relations to ...

and primary somatosensory cortex respectively. In general, the two hemispheres receive information from the opposite (contralateral) side of the 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 field. The organization of sensory maps in the cortex reflects that of the corresponding sensing organ, in what is known as a topographic map. Neighboring points in the primary visual cortex, for example, correspond to neighboring points in the retina. This topographic map is called a retinotopic map. In the same way, there exists a tonotopic map in the primary auditory cortex and a 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

homunculus A homunculus ( , , ; "little person") is a representation of a small human being, originally depicted as small statues made out of clay. Popularized in sixteenth-century alchemy and nineteenth-century fiction, it has historically referred to the ...

, 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 *

Supplementary motor area The supplementary motor area (SMA) is a part of the motor cortex of primates that contributes to the control of movement. It is located on the midline surface of the hemisphere just in front of (anterior to) the primary motor cortex leg representa ...

s and

premotor cortex The premotor cortex is an area of the motor cortex lying within the frontal lobe of the brain just anterior to the primary motor cortex. It occupies part of Brodmann's area 6. It has been studied mainly in primates, including monkeys and humans ...

, which ''select'' voluntary movements. In addition, motor functions have been described for: *

Posterior parietal cortex The posterior parietal cortex (the portion of parietal neocortex posterior to the primary somatosensory cortex) plays an important role in planned movements, spatial reasoning, and attention. Damage to the posterior parietal cortex can produce a ...

, 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 putamen (; from Latin, meaning "nutshell") is a round structure located at the base of the forebrain (telencephalon). The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that compose the basal ...

, 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 The lentiform nucleus, or lenticular nucleus, comprises the putamen and the globus pallidus within the basal ganglia. With the caudate nucleus, it forms the dorsal striatum. It is a large, lens-shaped mass of gray matter just lateral to the inter ...

, because together they form a lens-shaped body. The putamen and caudate nucleus are also collectively called the corpus striatum after their striped appearance.

Association areas

Cortical areas that have been shown to be involved in speech processing fnhum-06-00099-g005

The association areas are the parts of the cerebral cortex that do not belong to the primary regions. They function to produce a meaningful perceptual experience of the world, enable us to interact effectively, and support abstract thinking and language. The parietal, temporal, and

s – all located in the posterior part of the cortex – integrate sensory information and information stored in memory. The

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. 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 The inferior frontal gyrus (IFG), (gyrus frontalis inferior), is the lowest positioned gyrus of the frontal gyri, of the frontal lobe, and is part of the prefrontal cortex. Its superior border is the inferior frontal sulcus (which divides it f ...

, BA44 and BA45, for language expression and in Wernicke's 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 The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Va ...

Clinical significance

Neurodegenerative diseases such as Alzheimer's disease, show as a marker, an atrophy of the grey matter of the cerebral cortex. Other diseases of the central nervous system include neurological disorders such as epilepsy,

movement disorder Movement disorder refers to any clinical syndrome with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders are synonymous with basal ganglia or extrapyramidal ...

s, and 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 pathogens. The developing fetus is susceptible to a range of environmental factors that can cause birth defects and problems in later development. Maternal alcohol consumption for example can cause fetal alcohol spectrum disorder. Other factors that can cause neurodevelopment disorders are toxicants such as drugs, and exposure to radiation as from

X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

s. Infections can also affect the development of the cortex. A viral infection is one of the causes of

lissencephaly Lissencephaly (, meaning "smooth brain") is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in ...

, which results in a smooth cortex without

. A type of

electrocorticography Electrocorticography (ECoG), or intracranial electroencephalography (iEEG), is a type of electrophysiological monitoring that uses electrodes placed directly on the exposed surface of the brain to record electrical activity from the cerebral co ...

called

cortical stimulation mapping Cortical stimulation mapping (CSM) is a type of electrocorticography that involves a physically invasive procedure and aims to localize the function of specific brain regions through direct electrical stimulation of the cerebral cortex. It remains ...

is an invasive procedure that involves placing electrodes 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.

Genes associated with cortical disorders

There are a number of genetic mutations that can cause a wide range of genetic disorders of the cerebral cortex, including microcephaly, schizencephaly and types of

Chromosome abnormalities A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...

can also result causing a number of neurodevelopmental disorders such as fragile X syndrome and Rett syndrome.

MCPH1 Microcephalin (MCPH1) is a gene that is expressed during fetal brain development. Certain mutations in ''MCPH1'', when homozygous, cause primary microcephaly—a severely diminished brain. Hence, it has been assumed that variants have a role in ...

codes for microcephalin, and disorders in this and in ASPM are associated with microcephaly. Mutations in the gene

NBS1 Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the ''NBN'' gene. Function Nibrin is a protein associated with the repair of double strand breaks (DSBs) which pose serious damage to a genome. It is a 754 amino ac ...

that codes for

nibrin Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the ''NBN'' gene. Function Nibrin is a protein associated with the repair of double strand breaks (DSBs) which pose serious damage to a genome. It is a 754 amino ac ...

can cause Nijmegen breakage syndrome, characterised by microcephaly. Mutations in EMX2, and COL4A1 are associated with schizencephaly, a condition marked by the absence of large parts of the cerebral hemispheres.

History

In 1909,

distinguished different areas of the neocortex based on cytoarchitectural difference and divided the cerebral cortex into 52 regions. 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.

Other animals

The cerebral cortex is derived from the pallium, a layered structure found in the

forebrain In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the rostral (forward-most) portion of the brain. The forebrain (prosencephalon), the midbrain (mesencephalon), and hindbrain (rhombencephalon) are the three primary ...

of all vertebrates. 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 homologous to the neocortex, hippocampus, amygdala, and olfactory cortex, respectively. 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 The mushroom bodies or ''corpora pedunculata'' are a pair of structures in the brain of insects, other arthropods, and some annelids (notably the ragworm ''Platynereis dumerilii''). They are known to play a role in olfactory learning and memory ...

of the ragworm ''

Platynereis dumerilii ''Platynereis dumerilii'' is a species of annelid polychaete worm. It was originally placed into the genus ''Nereis'' and later reassigned to the genus '' Platynereis''. ''Platynereis dumerilii'' lives in coastal marine waters from temperate t ...

''. 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

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

References

External links

* *
"The primary visual cortex"
Webvision: Comprehensive article about the structure and function of the primary visual cortex.
"Basic cell types"
Webvision: Image of the basic cell types of the monkey cerebral cortex.
Cerebral Cortex - Cell Centered Database
{{DEFAULTSORT:Cerebral Cortex