The six-layeredneocortex makes up approximately 90% of thecortex, with theallocortex making up the remainder.[3] The cortex is divided into left and right parts by thelongitudinal fissure, which separates the twocerebral hemispheres that are joined beneath the cortex by thecorpus callosum. 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 thecranium. Apart from minimising brain and cranial volume,cortical folding is crucial for thebrain circuitry and its functional organisation.[4] In mammals with small brains, there is no folding and the cortex is smooth.[5][6]
A fold or ridge in the cortex is termed agyrus (plural gyri) and a groove is termed asulcus (plural sulci). These surface convolutions appear duringfetal development and continue to mature after birth through the process ofgyrification. In thehuman brain, the majority of the cerebral cortex is not visible from the outside, but buried in the sulci.[7] The major sulci and gyri mark the divisions of the cerebrum into thelobes of the brain. The four major lobes are thefrontal,parietal,occipital andtemporal lobes. Other lobes are thelimbic lobe, and theinsular cortex often referred to as theinsular lobe.
There are between 14 and 16 billionneurons in the human cerebral cortex.[2] These are organised into horizontal cortical layers, and radially intocortical columns andminicolumns. Cortical areas have specific functions such as movement in themotor cortex, and sight in thevisual cortex. The motor cortex is primarily located in theprecentral gyrus, and the visual cortex is located in the occipital lobe.
The cerebral cortex is the outer covering of the surfaces of the cerebral hemispheres and is folded into peaks calledgyri, and grooves calledsulci. In thehuman brain, it is between 2 and 3-4 mm. thick,[8] and makes up 40% of the brain's mass.[2] 90% of the cerebral cortex is the six-layeredneocortex whilst the other 10% is made up of the three/four-layeredallocortex.[2] There are between 14 and 16 billion neurons in the cortex.[2] These cortical neurons are organized radially incortical columns, andminicolumns, in the horizontally organized layers of the cortex.[9][10]
The neocortex is separable into different regions of cortex known in the plural as cortices, and include themotor cortex andvisual cortex. About two thirds of the cortical surface is buried in the sulci and theinsular cortex is completely hidden. The cortex is thickest over the top of a gyrus and thinnest at the bottom of a sulcus.[11]
The cerebral cortex is folded in a way that allows a large surface area ofneural tissue to fit within the confines of theneurocranium. When unfolded in the human, eachhemispheric cortex has a total surface area of about 0.12 square metres (1.3 sq ft).[12] The folding is inward away from the surface of the brain, and is also present on the medial surface of each hemisphere within thelongitudinal 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 smallrodents have smooth cerebral surfaces withoutgyrification.[6]
For species of mammals, larger brains (in absolute terms, not just in relation to body size) tend to have thicker cortices.[15] The smallest mammals, such asshrews, 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.[2][8] There is an approximatelylogarithmic relationship between brain weight and cortical thickness.[15]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.[16] One study has found some positive association between the cortical thickness andintelligence.[17]Another study has found that thesomatosensory cortex is thicker inmigraine 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.[18][19]A later study using a larger patient population reports no change in the cortical thickness in patients with migraine.[20]A genetic disorder of the cerebral cortex, whereby decreased folding in certain areas results in amicrogyrus, where there are four layers instead of six, is in some instances seen to be related todyslexia.[21]
Diagram of layers pattern. Cells grouped on left, axonal layers on right.Three drawings of cortical lamination bySantiago Ramon y Cajal, each showing a vertical cross-section, with the surface of the cortex at the top. Left:Nissl-stained visual cortex of a human adult. Middle: Nissl-stained motor cortex of a human adult. Right:Golgi-stained cortex of a1+1⁄2 month-old infant. The Nissl stain shows the cell bodies of neurons; the Golgi stain shows thedendrites and axons of a random subset of neurons.Micrograph showing thevisual cortex (predominantly pink). Subcorticalwhite matter (predominantly blue) is seen at the bottom of the image.HE-LFB stain.Golgi-stained neurons in the cortex (macaque)
Theneocortex is formed of six layers, numbered I to VI, from the outermost layer I – near to thepia mater, to the innermost layer VI – near to the underlyingwhite 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.
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 thelaminar structure of the cortex in different species. The work ofKorbinian Brodmann (1909) established that the mammalian neocortex is consistently divided into six layers.
Layer I is themolecular layer, and contains few scattered neurons, includingGABAergicrosehip neurons.[22] Layer I consists largely of extensions of apicaldendritic tufts ofpyramidal neurons and horizontally oriented axons, as well asglial cells.[4] During development,Cajal–Retzius cells[23] and subpial granular layer cells[24] are present in this layer. Also, some spinystellate cells can be found here. Inputs to the apical tufts are thought to be crucial for thefeedback interactions in the cerebral cortex involved in associative learning and attention.[25]
While it was once thought that the input to layer I came from the cortex itself,[26] it is now known that layer I across the cerebral cortex receives substantial input frommatrix or M-type thalamus cells,[27] as opposed tocore or C-type that go to layer IV.[28]
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.[29]
Layer III, theexternal 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 ofcommissural corticocorticalafferents, and layer III is the principal source of corticocorticalefferents.
Layer IV, theinternal granular layer, contains different types ofstellate and pyramidal cells, and is the main target ofthalamocortical afferents from thalamus type C neurons (core-type)[28] 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 elephants,cetaceans, andhippopotamus do not have a layer IV with axons which would terminate there going instead to the inner part of layer III.[30]
Layer V, theinternal pyramidal layer, contains large pyramidal neurons. Axons from these leave the cortex and connect with subcortical structures including thebasal ganglia. In the primary motor cortex of the frontal lobe, layer V contains giant pyramidal cells calledBetz cells, whose axons travel through theinternal capsule, thebrain stem, and the spinal cord forming thecorticospinal tract, which is the main pathway for voluntary motor control.
Layer VI, thepolymorphic layer ormultiform layer, contains few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons; layer VI sendsefferent fibers to the thalamus, establishing a very precise reciprocal interconnection between the cortex and the thalamus.[31] 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 sendexcitatory fibers to neurons in the thalamus and also send collaterals to thethalamic reticular nucleus thatinhibit these same thalamus neurons or ones adjacent to them.[32] One theory is that because the inhibitory output is reduced bycholinergic input to the cerebral cortex, this provides thebrainstem with adjustable "gain control for the relay oflemniscal inputs".[32]
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 intocortical columns andminicolumns.[33] It has been proposed that the minicolumns are the basic functional units of the cortex.[34] In 1957,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 andWiesel, 1959),[35] auditory cortex,and associative cortex.
Cortical areas that lack a layer IV are calledagranular. Cortical areas that have only a rudimentary layer IV are called dysgranular.[36] Information processing within each layer is determined by different temporal dynamics with that in layers II/III having a slow 2 Hzoscillation while that in layer V has a fast 10–15 Hz oscillation.[37]
Based on the differences inlaminar organization the cerebral cortex can be classified into two types, the large area ofneocortex which has six cell layers, and the much smaller area ofallocortex that has three or four layers:[3]
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 granularprimary motor cortex, and the striateprimary visual cortex. The neocortex has two subtypes, thetrue isocortex and theproisocortex 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, thepaleocortex with three cortical laminae, thearchicortex which has four or five, and a transitional area adjacent to the allocortex, theperiallocortex. Examples of allocortex are theolfactory cortex and thehippocampus.
There is a transitional area between the neocortex and the allocortex called theparalimbic 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 fourlobes: thefrontal lobe,temporal lobe, theparietal lobe, and theoccipital lobe, named from their overlying bones of the skull.
Arterial supply showing the regions supplied by the posterior, middle, and anteriorcerebral arteries.
Blood supply to the cerebral cortex is part of thecerebral circulation.Cerebral arteries supply the blood thatperfuses 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 theanterior cerebral artery, themiddle cerebral artery, and theposterior 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.
Thecircle of Willis is the main blood system that deals with blood supply in the cerebrum and cerebral cortex.
Theprenatal development of the cerebral cortex is a complex and finely tuned process calledcorticogenesis, influenced by the interplay between genes and the environment.[38]
The cerebral cortex develops from the most anterior part, the forebrain region, of theneural tube.[39][40] Theneural plate folds and closes to form theneural tube. From the cavity inside the neural tube develops theventricular system, and, from theneuroepithelial cells of its walls, theneurons andglia of the nervous system. The most anterior (front, or cranial) part of the neural plate, theprosencephalon, which is evident beforeneurulation begins, gives rise to the cerebral hemispheres and later cortex.[41]
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 fromradial glia migration that form the different cell types of the neocortex and it is a period associated with an increase inneurogenesis. 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 earlierprogenitors giving rise to any cell type in the cortex and later progenitors giving rise only toneurons 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 inS orG2 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.[43]
Although the majority of the cells that compose the cortex are derived locally from radial glia there is a subset population of neurons thatmigrate from other regions. Radial glia give rise to neurons that are pyramidal in shape and useglutamate as aneurotransmitter, however these migrating cells contribute neurons that are stellate-shaped and useGABA as their main neurotransmitter. These GABAergic neurons are generated by progenitor cells in themedial ganglionic eminence (MGE) that migrate tangentially to the cortex via thesubventricular zone. This migration of GABAergic neurons is particularly important sinceGABA 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 thathyperpolarizespostsynaptic neurons.[44]The glial fibers produced in the first divisions of the progenitor cells are radially oriented, spanning the thickness of the cortex from theventricular zone to the outer,pial surface, and provide scaffolding for the migration of neurons outwards from theventricular zone.[45][46]
At birth there are very fewdendrites 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 thousandsynaptic connections with other neurons. The axon can develop to extend a long way from the cell body.[47]
The first divisions of the progenitor cells are symmetric, which duplicates the total number of progenitor cells at eachmitotic cycle. Then, some progenitor cells begin to divide asymmetrically, producing one postmitotic cell that migrates along the radial glial fibers, leaving theventricular zone, and one progenitor cell, which continues to divide until the end of development, when it differentiates into aglial cell or anependymal cell. As theG1 phase ofmitosis is elongated, in what is seen as selective cell-cycle lengthening, the newly born neurons migrate to more superficial layers of the cortex.[48] The migrating daughter cells become thepyramidal cells of the cerebral cortex.[49] The development process is time ordered and regulated by hundreds of genes andepigenetic regulatory mechanisms.[50]
Human cortical development between 26 and 39 week gestational age
Thelayered structure of the mature cerebral cortex is formed during development. The first pyramidal neurons generated migrate out of theventricular zone andsubventricular zone, together withreelin-producingCajal–Retzius neurons, from thepreplate. Next, a cohort of neurons migrating into the middle of the preplate divides this transient layer into the superficialmarginal zone, which will become layer I of the mature neocortex, and thesubplate,[51] forming a middle layer called thecortical 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.[52] The only exception to this inside-out sequence ofneurogenesis occurs in the layer I ofprimates, in which, in contrast torodents, neurogenesis continues throughout the entire period ofcorticogenesis.[53]
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',[54] which is regulated by molecular signals such asfibroblast growth factorFGF8 early in embryonic development.[55][56] These signals regulate the size, shape, and position of cortical areas on the surface of the cortical primordium, in part by regulating gradients oftranscription factor expression, through a process calledcortical patterning. Examples of such transcription factors include the genesEMX2 andPAX6.[57] Together, bothtranscription factors form an opposing gradient of expression.Pax6 is highly expressed at therostral lateral pole, whileEmx2 is highly expressed in thecaudomedial 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 thevisual cortex. On the contrary, if mutations in Emx2 occur, it can cause the Pax6-expressing domain to expand and result in thefrontal andmotor cortical regions enlarging. Therefore, researchers believe that similar gradients andsignaling centers next to the cortex could contribute to the regional expression of these transcription factors.[44]Two very well studied patterning signals for the cortex includeFGF andretinoic acid. If FGFs aremisexpressed in different areas of the developing cortex,cortical patterning is disrupted. Specifically, whenFgf8 is increased in theanterior pole, Emx2 isdownregulated and acaudal 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.[44]
Rapid expansion of the cortical surface area is regulated by the amount of self-renewal ofradial glial cells and is partly regulated byFGF andNotch genes.[58] During the period of cortical neurogenesis and layer formation, many higher mammals begin the process ofgyrification, which generates the characteristic folds of the cerebral cortex.[59][60] Gyrification is regulated by a DNA-associated proteinTrnp1[61] and by FGF andSHH signaling.[62][63]
Of all the different brain regions, the cerebral cortex shows the largest evolutionary variation and has evolved most recently.[6] In contrast to the highly conserved circuitry of themedulla 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.[6]
A key theory of cortical evolution is embodied in theradial unit hypothesis and relatedprotomap hypothesis, first proposed by Rakic.[64] This theory states that new cortical areas are formed by the addition of new radial units, which is accomplished at thestem cell level. The protomap hypothesis states that the cellular and molecular identity and characteristics of neurons in each cortical area are specified by corticalstem cells, known asradial glial cells, in a primordial map. This map is controlled by secreted signalingproteins and downstreamtranscription factors.[65][66][67]
The cerebral cortex is connected to various subcortical structures such as thethalamus and thebasal ganglia, sending information to them alongefferent connections and receiving information from them viaafferent connections. Most sensory information is routed to the cerebral cortex via the thalamus. Olfactory information, however, passes through theolfactory 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;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.[68]
The whole of the cerebral cortex was divided into 52 different areas in an early presentation byKorbinian Brodmann. These areas, known asBrodmann areas, are based on theircytoarchitecture but also relate to various functions. An example is Brodmann area 17, which is theprimary visual cortex.
In more general terms the cortex is typically described as comprising three parts: sensory, motor, and association areas.
The sensory areas are the cortical areas that receive and process information from thesenses. Parts of the cortex that receive sensory inputs from thethalamus are called primary sensory areas. The senses of vision, hearing, and touch are served by the primary visual cortex, primaryauditory cortex andprimary somatosensory cortex respectively. In general, the two hemispheres receive information from the opposite (contralateral) side of thebody. For example, the right primary somatosensory cortex receives information from the left limbs, and the right visual cortex receives information from the left visualfield.
The organization of sensory maps in the cortex reflects that of the corresponding sensing organ, in what is known as atopographic map. Neighboring points in the primaryvisual cortex, for example, correspond to neighboring points in theretina. This topographic map is called aretinotopic map. In the same way, there exists atonotopic map in the primary auditory cortex and asomatotopic map in the primary sensory cortex. This last topographic map of the body onto theposterior central gyrus has been illustrated as a deformed human representation, the somatosensoryhomunculus, 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.
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:
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 calledbasal 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 thecaudate nucleus, theputamen, theglobus pallidus, thesubstantia nigra, thenucleus accumbens, and thesubthalamic nucleus. The putamen and globus pallidus are also collectively known as thelentiform nucleus, because together they form a lens-shaped body. The putamen and caudate nucleus are also collectively called thecorpus striatum after their striped appearance.[71][72]
The association areas are the parts of the cerebral cortex that do not belong to the primary regions. They function to produce a meaningfulperceptual experience of the world, enable us to interact effectively, and support abstract thinking and language. Theparietal,temporal, andoccipital lobes – all located in the posterior part of the cortex – integrate sensory information and information stored in memory. Thefrontal 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.[73] 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 inBroca's area in areas of the leftinferior frontal gyrus,BA44 andBA45, for language expression and inWernicke's areaBA22, for language reception. However, the processes of language expression and reception have been shown to occur in areas other than just those structures around thelateral sulcus, including the frontal lobe,basal ganglia,cerebellum, andpons.[74]
Hemodynamic changes observed on gyrencephalic brain cortex after an arterial vessel occlusion in IOS. The video has a speed of 50x to better appreciate thespreading 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.[75] https://doi.org/10.1007/s00701-019-04132-8
Brain damage from disease or trauma, can involve damage to a specific lobe such as infrontal lobe disorder, and associated functions will be affected. Theblood–brain barrier that serves to protect the brain from infection can become compromised allowing entry topathogens.
Thedeveloping fetus is susceptible to a range of environmental factors that can causebirth defects and problems in later development. Maternal alcohol consumption for example can causefetal alcohol spectrum disorder.[77] Other factors that can cause neurodevelopment disorders aretoxicants such asdrugs, and exposure toradiation as fromX-rays. Infections can also affect the development of the cortex. A viral infection is one of the causes oflissencephaly, which results in a smooth cortex withoutgyrification.
A type ofelectrocorticography calledcortical stimulation mapping is an invasive procedure that involves placingelectrodes 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.[78]
In 1909,Korbinian Brodmann distinguished 52 different regions of the cerebral cortex based on their cytoarchitecture. These are known asBrodmann areas.[82]
The cerebral cortex is derived from thepallium, a layered structure found in theforebrain of allvertebrates. 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 behomologous to theneocortex,hippocampus,amygdala, andolfactory cortex, respectively.
Inavian brains, evidence suggests theavian pallium's neuroarchitecture to be reminiscent of the mammalian cerebral cortex.[83] The avian pallium has also been suggested to be an equivalent neural basis forconsciousness.[84][85]
Until recently no counterpart to the cerebral cortex had been recognized in invertebrates. However, a study published in the journalCell in 2010, based on gene expression profiles, reported strong affinities between the cerebral cortex and themushroom bodies of theragwormPlatynereis dumerilii.[86] 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 thePrecambrian era.
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