View source for Biology:Human brain

{{Short description|Central organ of the human nervous system}}
{{Infobox anatomy
| Name       = Human brain
| Latin      = encephalon
| Greek      = ἐγκέφαλος (enképhalos)<ref>{{cite encyclopedia |url=http://etymonline.com/index.php?allowed_in_frame=0&search=encephalo- |title=''Encephalo-'' Etymology |dictionary=Online Etymology Dictionary |access-date=October 24, 2015 |url-status=live |archive-url=https://web.archive.org/web/20171002022623/http://etymonline.com/index.php?allowed_in_frame=0&search=encephalo- |archive-date=October 2, 2017  }}</ref>
| Image      = Brain autopsy lateral view.jpg
| Caption    = The human brain, obtained after an [[Medicine:Autopsy|autopsy]]
| Image2     = Skull and brain normal human.svg
| Caption2   = Human brain and skull
| Precursor  = [[Biology:Neural tube|Neural tube]]
| System     = [[Biology:Central nervous system|Central nervous system]]
| Artery     = Internal carotid arteries, vertebral arteries
| Vein       = [[Medicine:Internal jugular vein|Internal jugular vein]], internal cerebral veins;<br />external veins: (superior, middle, and inferior cerebral veins), basal vein, and cerebellar veins
| Nerve      =
| Lymph      =
}}

The '''brain''' is the central [[Biology:Organ (anatomy)|organ]] of the human [[Biology:Nervous system|nervous system]], and with the [[Biology:Spinal cord|spinal cord]] makes up the [[Biology:Central nervous system|central nervous system]]. The brain consists of the [[Biology:Cerebrum|cerebrum]], the [[Biology:Brainstem|brainstem]] and the [[Biology:Cerebellum|cerebellum]]. It controls most of the activities of the [[Medicine:Human body|body]], processing, integrating, and coordinating the information it receives from the [[Biology:Sensory nervous system|sense organs]], and making decisions as to the instructions sent to the rest of the body. The brain is contained in, and protected by, the [[Medicine:Neurocranium|skull bones]] of the [[Medicine:Human head|head]].

The cerebrum, the largest part of the human brain, consists of two [[Biology:Cerebral hemisphere|cerebral hemisphere]]s. Each hemisphere has an inner core composed of [[Biology:White matter|white matter]], and an outer surface – the [[Biology:Cerebral cortex|cerebral cortex]] – composed of [[Biology:Grey matter|grey matter]]. The cortex has an outer layer, the [[Biology:Neocortex|neocortex]], and an inner [[Biology:Allocortex|allocortex]]. The neocortex is made up of six [[Biology:Cerebral cortex#Layers of neocortex|neuronal layers]], while the allocortex has three or four. Each hemisphere is conventionally divided into four [[Biology:Lobes of the brain|lobes]] – the [[Biology:Frontal lobe|frontal]], [[Biology:Temporal lobe|temporal]], [[Biology:Parietal lobe|parietal]], and [[Biology:Occipital lobe|occipital lobe]]s. The frontal lobe is associated with [[Philosophy:Executive functions|executive functions]] including [[Philosophy:Self-control|self-control]], [[Engineering:Planning|planning]], [[Philosophy:Reason|reason]]ing, and [[Philosophy:Abstraction|abstract thought]], while the [[Biology:Occipital lobe|occipital lobe]] is dedicated to vision. Within each lobe, cortical areas are associated with specific functions, such as the [[Biology:Sensory cortex|sensory]], [[Biology:Motor cortex|motor]] and [[Biology:Cerebral cortex#Association areas|association]] regions. Although the left and right hemispheres are broadly similar in shape and function, some functions are [[Biology:Lateralization of brain function|associated with one side]], such as [[Social:Language|language]] in the left and [[Physics:Spatial visualization ability|visual-spatial ability]] in the right. The hemispheres are connected by [[Biology:Commissural fiber|commissural nerve tracts]], the largest being the [[Biology:Corpus callosum|corpus callosum]].

The cerebrum is connected by the brainstem to the spinal cord. The brainstem consists of the [[Biology:Midbrain|midbrain]], the [[Biology:Pons|pons]], and the medulla oblongata. The [[Biology:Cerebellum|cerebellum]] is connected to the brainstem by three pairs of [[Biology:Nerve tract|nerve tract]]s called cerebellar peduncles. Within the cerebrum is the [[Biology:Ventricular system|ventricular system]], consisting of four interconnected [[Biology:Ventricular system#Structure|ventricles]] in which [[Biology:Cerebrospinal fluid|cerebrospinal fluid]] is produced and circulated. Underneath the cerebral cortex are several important structures, including the [[Biology:Thalamus|thalamus]], the [[Biology:Epithalamus|epithalamus]], the [[Biology:Pineal gland|pineal gland]], the [[Biology:Hypothalamus|hypothalamus]], the [[Medicine:Pituitary gland|pituitary gland]], and the [[Biology:Subthalamus|subthalamus]]; the [[Philosophy:Limbic system|limbic structures]], including the amygdalae and the [[Biology:Hippocampus|hippocampi]], the [[Biology:Claustrum|claustrum]], the various [[Biology:Nucleus (neuroanatomy)|nuclei]] of the [[Biology:Basal ganglia|basal ganglia]], the [[Biology:Basal forebrain|basal forebrain]] structures, and the three circumventricular organs. Brain structures that are not on the midplane exist in pairs, so there are for example two hippocampi and two amygdalae. The [[Biology:Brain cell|cells of the brain]] include [[Biology:Neuron|neuron]]s and supportive glial cells. There are more than 86 billion neurons in the brain, and a more or less equal number of other cells. Brain activity is made possible by the interconnections of neurons and their release of [[Biology:Neurotransmitter|neurotransmitter]]s in response to [[Biology:Action potential|nerve impulses]]. Neurons connect to form [[Biology:Neural pathway|neural pathway]]s, [[Neural circuit|neural circuit]]s, and elaborate [[Biology:Large-scale brain networks|network systems]]. The whole circuitry is driven by the process of [[Biology:Neurotransmission|neurotransmission]].

The brain is protected by the [[Biology:Skull|skull]], suspended in [[Biology:Cerebrospinal fluid|cerebrospinal fluid]], and isolated from the [[Biology:Circulatory system|bloodstream]] by the [[Biology:Blood–brain barrier|blood–brain barrier]]. However, the brain is still susceptible to [[Medicine:Brain damage|damage]], disease, and [[Medicine:Infection|infection]]. Damage can be caused by trauma, or a loss of blood supply known as a [[Medicine:Stroke|stroke]]. The brain is susceptible to [[Medicine:Neurodegeneration|degenerative disorders]], such as [[Medicine:Parkinson's disease|Parkinson's disease]], [[Medicine:Dementia|dementia]]s including [[Medicine:Alzheimer's disease|Alzheimer's disease]], and multiple sclerosis. Psychiatric conditions, including [[Medicine:Schizophrenia|schizophrenia]] and clinical depression, are thought to be associated with brain dysfunctions. The brain can also be the site of tumours, both benign and [[Medicine:Cancer|malignant]]; these mostly [[Medicine:Metastasis|originate from other sites in the body]].

The study of the anatomy of the brain is [[Biology:Neuroanatomy|neuroanatomy]], while the study of its function is [[Biology:Neuroscience|neuroscience]]. Numerous techniques are used to study the brain. [[Biology:Biological specimen|Specimens]] from other animals, which may be [[Biology:Histology|examined microscopically]], have traditionally provided much information. [[Medicine:Medical imaging|Medical imaging]] technologies such as [[Biology:Functional neuroimaging|functional neuroimaging]], and [[Biology:Electroencephalography|electroencephalography]] (EEG) recordings are important in studying the brain. The [[Medicine:Medical history|medical history]] of people with [[Medicine:Brain damage|brain injury]] has provided insight into the function of each part of the brain. Neuroscience research has expanded considerably, and research is ongoing.

In culture, the [[Philosophy:Philosophy of mind|philosophy of mind]] has for centuries attempted to address the question of the nature of [[Philosophy:Consciousness|consciousness]] and the [[Philosophy:Mind–body problem|mind–body problem]]. The [[Unsolved:Pseudoscience|pseudoscience]] of [[Philosophy:Phrenology|phrenology]] attempted to localise personality attributes to regions of the cortex in the 19th century. [[Engineering:Brain transplant#In science fiction|In science fiction, brain transplants]] are imagined in tales such as the 1942 ''Donovan's Brain''.

==Structure==
[[File:Human brain.jpg|thumb|Human brain (sagittal section)]]

=== Gross anatomy ===
The adult human brain weighs on average about {{convert|1.2-1.4|kg|abbr=on}} which is about 2% of the total body weight,<ref name=CarpenterCh1>{{cite book |title=Carpenter's Human Neuroanatomy |last1=Parent |first1=A. |last2=Carpenter |first2=M.B. |publisher=Williams & Wilkins |year=1995 |isbn=978-0-683-06752-1 |chapter=Ch. 1}}</ref><ref name="Bigos">{{cite book |last1=Bigos |first1=K.L. |last2=Hariri |first2=A. |last3=Weinberger |first3=D. |title=Neuroimaging Genetics: Principles and Practices |publisher=[[Organization:Oxford University Press|Oxford University Press]] |isbn=978-0-19-992022-8 |year=2015 |page=157 |url=https://books.google.com/books?id=TF_iCgAAQBAJ&pg=PA157}}</ref> with a volume of around 1260&nbsp;[[Cubic centimetre|cm<sup>3</sup>]] in men and 1130&nbsp;cm<sup>3</sup> in women.<ref name=Cosgrove>{{cite journal |last1=Cosgrove |first1=K.P. |last2=Mazure |first2=C.M. |last3=Staley |first3=J.K. |title=Evolving knowledge of sex differences in brain structure, function, and chemistry |year=2007 |journal=Biol Psychiatry |volume=62 |pages=847–855 |pmid=17544382 |pmc=2711771 |doi=10.1016/j.biopsych.2007.03.001 |issue=8}}</ref> There is substantial individual variation,<ref name=Cosgrove/> with the standard [[Reference range|reference range]] for men being {{convert|1180-1620|g|lb|abbr=on}}<ref name="MolinaDiMaio2012">{{cite journal|last1=Molina|first1=D. Kimberley|last2=DiMaio|first2=Vincent J.M.|title=Normal Organ Weights in Men|journal=The American Journal of Forensic Medicine and Pathology|volume=33|issue=4|year=2012|pages=368–372|issn=0195-7910|doi=10.1097/PAF.0b013e31823d29ad|pmid=22182984|s2cid=32174574}}</ref> and for women {{convert|1030-1400|g|lb|abbr=on}}.<ref name="MolinaDiMaio2015">{{cite journal|last1=Molina|first1=D. Kimberley|last2=DiMaio|first2=Vincent J. M.|title=Normal Organ Weights in Women|journal=The American Journal of Forensic Medicine and Pathology|volume=36|issue=3|year=2015|pages=182–187|issn=0195-7910|doi=10.1097/PAF.0000000000000175|pmid=26108038|s2cid=25319215}}</ref>

The [[Biology:Cerebrum|cerebrum]], consisting of the [[Biology:Cerebral hemisphere|cerebral hemisphere]]s, forms the largest part of the brain and overlies the other brain structures.{{sfn|Gray's Anatomy|2008|pp=227-9}} The outer region of the hemispheres, the [[Biology:Cerebral cortex|cerebral cortex]], is [[Biology:Grey matter|grey matter]], consisting of [[Biology:Cerebral cortex#Layers|cortical layers]] of [[Biology:Neuron|neuron]]s. Each hemisphere is divided into four main [[Biology:Lobes of the brain|lobes]] – the [[Biology:Frontal lobe|frontal lobe]], [[Biology:Parietal lobe|parietal lobe]], [[Biology:Temporal lobe|temporal lobe]], and [[Biology:Occipital lobe|occipital lobe]].{{sfn|Gray's Anatomy|2008|pp=335-7}} Three other lobes are included by some sources which are a ''central lobe'', a [[Biology:Limbic lobe|limbic lobe]], and an [[Biology:Insular cortex|insular lobe]].<ref name="Ribas">{{cite journal |page=7 |pmid=20121437|year=2010|last1=Ribas|first1=G. C.|title=The cerebral sulci and gyri|journal=Neurosurgical Focus|volume=28|issue=2|doi=10.3171/2009.11.FOCUS09245|doi-access=free}}</ref> The central lobe comprises the [[Biology:Precentral gyrus|precentral gyrus]] and the [[Biology:Postcentral gyrus|postcentral gyrus]] and is included since it forms a distinct functional role.<ref name="Ribas"/><ref name="Frigeri">{{cite journal |pmid=25555079|year=2015|last1=Frigeri|first1=T.|title=Microsurgical anatomy of the central lobe|journal=Journal of Neurosurgery|volume=122|issue=3|pages=483–98|last2=Paglioli|first2=E.|last3=De Oliveira|first3=E.|last4=Rhoton Jr|first4=A. L.|doi=10.3171/2014.11.JNS14315 }}</ref>

The [[Biology:Brainstem|brainstem]], resembling a stalk, attaches to and leaves the cerebrum at the start of the [[Biology:Midbrain|midbrain]] area. The brainstem includes the midbrain, the [[Biology:Pons|pons]], and the medulla oblongata. Behind the brainstem is the [[Biology:Cerebellum|cerebellum]] ({{lang-la |little brain}}).{{sfn|Gray's Anatomy|2008|pp=227-9}}

The cerebrum, brainstem, cerebellum, and spinal cord are covered by four<ref>{{cite journal |title=A mesothelium divides the subarachnoid space into functional compartments |bibcode-access=free |doi-access=free |journal=Science |year=2023 |volume=379 |doi=10.1126/science.adc8810 |url=https://www.researchgate.net/publication/366903551 |last1=Møllgård |first1=Kjeld |last2=Beinlich |first2=Felix R. M. |last3=Kusk |first3=Peter |last4=Miyakoshi |first4=Leo M. |last5=Delle |first5=Christine |last6=Plá |first6=Virginia |last7=Hauglund |first7=Natalie L. |last8=Esmail |first8=Tina |last9=Rasmussen |first9=Martin K. |last10=Gomolka |first10=Ryszard S. |last11=Mori |first11=Yuki |last12=Nedergaard |first12=Maiken |issue=6627 |pages=84–88 |pmid=36603070 |bibcode=2023Sci...379...84M |s2cid=255440992 }}
*{{cite news |title=Newly discovered anatomy shields and monitors brain |url=https://medicalxpress.com/news/2023-01-newly-anatomy-shields-brain.html |access-date=15 February 2023 |author=University of Rochester Medical Center |website=Medical Xpress |date=January 5, 2023 |language=en |archive-date=7 January 2023 |archive-url=https://web.archive.org/web/20230107034340/https://medicalxpress.com/news/2023-01-newly-anatomy-shields-brain.html |url-status=live }}</ref> membranes called [[Medicine:Meninges|meninges]]. The membranes are the tough [[Medicine:Dura mater|dura mater]]; the middle arachnoid mater and the more delicate inner pia mater. Between the arachnoid mater and the pia mater is the [[Medicine:Meninges#Subarachnoid space|subarachnoid space]] and subarachnoid cisterns, which contain the [[Biology:Cerebrospinal fluid|cerebrospinal fluid]].{{sfn|Purves|2012|p=724}} The outermost membrane of the cerebral cortex is the basement membrane of the pia mater called the [[Biology:Glia limitans|glia limitans]] and is an important part of the [[Biology:Blood–brain barrier|blood–brain barrier]].<ref name="Anatomy and Ultrastructure">{{Cite book |last1=Cipolla |first1=M.J. |chapter=Anatomy and Ultrastructure |title=The Cerebral Circulation |via=NCBI Bookshelf |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK53086/#s2.2 |publisher=Morgan & Claypool Life Sciences |date=January 1, 2009 |url-status=live |archive-url=https://web.archive.org/web/20171001170945/https://www.ncbi.nlm.nih.gov/books/NBK53086/#s2.2 |archive-date=October 1, 2017  }}</ref>
The living brain is very soft, having a gel-like consistency similar to soft tofu.<ref name="NPR">{{cite news |title=A Surgeon's-Eye View of the Brain |url=https://www.npr.org/templates/story/story.php?storyId=5396115 |website=NPR |series= Fresh Air |date=May 10, 2006 |url-status=live |archive-url=https://web.archive.org/web/20171107023155/http://www.npr.org/templates/story/story.php?storyId=5396115 |archive-date=November 7, 2017  }}</ref> The cortical layers of neurons constitute much of the cerebral [[Biology:Grey matter|grey matter]], while the deeper subcortical regions of [[Biology:Myelin|myelin]]ated [[Biology:Axon|axon]]s, make up the [[Biology:White matter|white matter]].{{sfn|Gray's Anatomy|2008|pp=227-9}} The white matter of the brain makes up about half of the total brain volume.<ref name="Neuron">{{cite journal |last1=Sampaio-Baptista |first1=C |last2=Johansen-Berg |first2=H |title=White Matter Plasticity in the Adult Brain |doi-access=free |journal=Neuron |date=December 20, 2017 |volume=96 |issue=6 |pages=1239–1251 |doi=10.1016/j.neuron.2017.11.026 |pmid=29268094|pmc=5766826 }}</ref>
{{multiple image
<!-- Layout parameters -->| align             = center
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<!-- Header -->| header_align      = center
| header            = Structural and functional areas of the human brain

<!--image 1-->| image1            = Sobo 1909 624.png
| width1            = 3060
| height1           = 2247
| alt1              = A diagram showing various structures within the human brain
| caption1          = Human brain bisected in the [[Biology:Sagittal plane|sagittal plane]], showing the white matter of the corpus callosum

<!--image 2-->| image2            = Blausen 0102 Brain Motor&Sensory (flipped).png
| width2            = 1425
| height2           = 951
| alt2              = A diagram of the functional areas of the human brain
| caption2          = Functional areas of the human brain. Dashed areas shown are commonly left hemisphere dominant.
}}

====Cerebrum====
{{Main|Biology:Cerebrum|Biology:Cerebral cortex}}
[[File:Gray726.png|thumb|Major gyri and sulci on the lateral surface of the cortex]]
[[File:Gehirn, medial - Lobi en.svg|thumb|Lobes of the brain]]

The cerebrum is the largest part of the brain and is divided into nearly [[Biology:Symmetry in biology#Bilateral symmetry|symmetrical]] left and right [[Biology:Cerebral hemisphere|hemisphere]]s by a deep groove, the [[Biology:Longitudinal fissure|longitudinal fissure]].<ref name="Davey">{{cite book |author=Davey, G. |title=Applied Psychology |isbn=978-1-4443-3121-9 |publisher={{wipe|John Wiley & Sons}} |year=2011 |page=153 |url=https://books.google.com/books?id=K1qq1SsgoxUC&pg=PA153}}</ref> Asymmetry between the lobes is noted as a [[Biology:Paleoneurobiology#Asymmetry|petalia]].<ref>{{cite journal|pmid=30601110|year=2019|last1=Arsava|first1=E. Y.|title=Occipital petalia as a predictive imaging sign for transverse sinus dominance|journal=Neurological Research|volume=41|issue=4|pages=306–311|last2=Arsava|first2=E. M.|last3=Oguz|first3=K. K.|last4=Topcuoglu|first4=M. A.|doi=10.1080/01616412.2018.1560643|s2cid=58546404}}</ref> The hemispheres are connected by five [[Biology:Commissural fiber#Structure|commissures]] that span the longitudinal fissure, the largest of these is the [[Biology:Corpus callosum|corpus callosum]].{{sfn|Gray's Anatomy|2008|pp=227-9}}
Each hemisphere is conventionally divided into four main [[Biology:Lobes of the brain|lobes]]; the [[Biology:Frontal lobe|frontal lobe]], [[Biology:Parietal lobe|parietal lobe]], [[Biology:Temporal lobe|temporal lobe]], and [[Biology:Occipital lobe|occipital lobe]], named according to the [[Biology:Skull|skull bones]] that overlie them.{{sfn|Gray's Anatomy|2008|pp=335-7}} Each lobe is associated with one or two specialised functions though there is some functional overlap between them.<ref name=Ackerman/> The surface of the brain is [[Biology:Gyrification|folded]] into ridges ([[Biology:Gyrus|gyri]]) and grooves ([[Biology:Sulcus (neuroanatomy)|sulci]]), many of which are named, usually according to their position, such as the [[Biology:Frontal gyrus|frontal gyrus]] of the frontal lobe or the [[Biology:Central sulcus|central sulcus]] separating the central regions of the hemispheres. There are many small variations in the secondary and tertiary folds.{{sfn|Larsen|2001|pp=455–456}}

The outer part of the cerebrum is the [[Biology:Cerebral cortex|cerebral cortex]], made up of [[Biology:Grey matter|grey matter]] arranged in layers. It is {{convert|2 |to |4 |mm}} thick, and deeply folded to give a convoluted appearance.<ref>{{cite book |last=Kandel |first=E.R. |author2=Schwartz, J.H. |author3=Jessel T.M. |title=Principles of Neural Science |year=2000 |publisher=McGraw-Hill Professional |isbn=978-0-8385-7701-1 |page=[https://archive.org/details/isbn_9780838577011/page/324 324] |url=https://archive.org/details/isbn_9780838577011/page/324 }}</ref> Beneath the cortex is the cerebral [[Biology:White matter|white matter]]. The largest part of the cerebral cortex is the [[Biology:Neocortex|neocortex]], which has six neuronal layers. The rest of the cortex is of [[Biology:Allocortex|allocortex]], which has three or four layers.{{sfn|Gray's Anatomy|2008|pp=227–9}}

The cortex is [[Biology:Brain mapping|mapped]] by divisions into about fifty different functional areas known as Brodmann's areas. These areas are distinctly different when [[Biology:Histology|seen under a microscope]].{{sfn|Guyton & Hall|2011|p=574}} The cortex is divided into two main functional areas – a [[Biology:Motor cortex|motor cortex]] and a [[Biology:Sensory cortex|sensory cortex]].{{sfn|Guyton & Hall|2011|p=667}} The [[Biology:Primary motor cortex|primary motor cortex]], which sends axons down to motor neurons in the brainstem and spinal cord, occupies the rear portion of the frontal lobe, directly in front of the somatosensory area. The [[Biology:Primary sensory areas|primary sensory areas]] receive signals from the [[Biology:Sensory nerve|sensory nerve]]s and [[Biology:Nerve tract|tracts]] by way of [[Biology:Thalamus#Thalamic nuclei|relay nuclei]] in the [[Biology:Thalamus|thalamus]]. Primary sensory areas include the [[Biology:Visual cortex|visual cortex]] of the [[Biology:Occipital lobe|occipital lobe]], the [[Biology:Auditory cortex|auditory cortex]] in parts of the [[Biology:Temporal lobe|temporal lobe]] and [[Biology:Insular cortex|insular cortex]], and the somatosensory cortex in the [[Biology:Parietal lobe|parietal lobe]]. The remaining parts of the cortex are called the association areas. These areas receive input from the sensory areas and lower parts of the brain and are involved in the complex [[Cognition|cognitive processes]] of [[Perception|perception]], [[Philosophy:Thought|thought]], and [[Decision-making|decision-making]].<ref>Principles of Anatomy and Physiology 12th Edition – Tortora, p. 519.</ref> The main functions of the frontal lobe are to [[Biology:Attentional control|control attention]], abstract thinking, behaviour, problem-solving tasks, and physical reactions and personality.<ref name="Freberg">{{cite book |author=Freberg, L. |title=Discovering Biological Psychology |publisher=Cengage Learning |year=2009 |pages=44–46 |isbn=978-0-547-17779-3 |url=https://books.google.com/books?id=-zyTMXAjzQsC&pg=PA44}}</ref><ref name="Kolb">{{cite book |last1=Kolb |first1=B. |last2=Whishaw |first2=I. |title=Fundamentals of Human Neuropsychology |publisher=Macmillan |year=2009 |pages=73–75 |isbn=978-0-7167-9586-5 |url=https://books.google.com/books?id=z0DThNQqdL4C&pg=PA73}}</ref> The occipital lobe is the smallest lobe; its main functions are visual reception, visual-spatial processing, movement, and [[Color vision#Color in the human brain|colour recognition]].<ref name="Freberg"/><ref name="Kolb"/> There is a smaller occipital lobule in the lobe known as the [[Biology:Cuneus|cuneus]]. The temporal lobe controls [[Biology:Echoic memory|auditory]] and visual memories, [[Biology:Language processing in the brain|language]], and some hearing and speech.<ref name="Freberg"/>

[[File:Visible Human head slice.jpg|thumb|upright|Cortical folds and white matter in horizontal bisection of head]]

<!--Ventricles and subcortical detail is here.-->The cerebrum contains the [[Biology:Ventricular system|ventricles]] where the cerebrospinal fluid is produced and circulated. Below the corpus callosum is the [[Biology:Septum pellucidum|septum pellucidum]], a membrane that separates the lateral ventricles. Beneath the lateral ventricles is the [[Biology:Thalamus|thalamus]] and to the front and below is the [[Biology:Hypothalamus|hypothalamus]]. The hypothalamus leads on to the [[Medicine:Pituitary gland|pituitary gland]]. At the back of the thalamus is the brainstem.{{sfn|Pocock|2006|p=64}}

The [[Biology:Basal ganglia|basal ganglia]], also called basal nuclei, are a set of structures deep within the hemispheres involved in behaviour and movement regulation.{{sfn|Purves|2012|p=399}} The largest component is the [[Biology:Striatum|striatum]], others are the [[Biology:Globus pallidus|globus pallidus]], the [[Biology:Substantia nigra|substantia nigra]] and the [[Biology:Subthalamic nucleus|subthalamic nucleus]].{{sfn|Purves|2012|p=399}} The striatum is divided into a ventral striatum, and dorsal striatum, subdivisions that are based upon function and connections. The ventral striatum consists of the [[Biology:Nucleus accumbens|nucleus accumbens]] and the [[Biology:Olfactory tubercle|olfactory tubercle]] whereas the dorsal striatum consists of the [[Biology:Caudate nucleus|caudate nucleus]] and the [[Biology:Putamen|putamen]]. The putamen and the globus pallidus lie separated from the lateral ventricles and thalamus by the [[Biology:Internal capsule|internal capsule]], whereas the caudate nucleus stretches around and abuts the lateral ventricles on their outer sides.{{sfn|Gray's Anatomy|2008|pp=325-6}} At the deepest part of the [[Biology:Lateral sulcus|lateral sulcus]] between the [[Biology:Insular cortex|insular cortex]] and the striatum is a thin neuronal sheet called the [[Biology:Claustrum|claustrum]].<ref name="Goll">{{cite journal |last1=Goll |first1=Y. |last2=Atlan |first2=G. |last3=Citri |first3=A. |title=Attention: the claustrum |journal=Trends in Neurosciences |date=August 2015 |volume=38 |issue=8 |pages=486–95 |doi=10.1016/j.tins.2015.05.006 |pmid=26116988|s2cid=38353825 }}</ref>

Below and in front of the striatum are a number of [[Biology:Basal forebrain|basal forebrain]] structures. These include the [[Biology:Nucleus basalis|nucleus basalis]], [[Biology:Diagonal band of Broca|diagonal band of Broca]], [[Biology:Substantia innominata|substantia innominata]], and the [[Biology:Medial septal nucleus|medial septal nucleus]]. These structures are important in producing the [[Biology:Neurotransmitter|neurotransmitter]], [[Chemistry:Acetylcholine|acetylcholine]], which is then distributed widely throughout the brain. The basal forebrain, in particular the nucleus basalis, is considered to be the major [[Biology:Cholinergic|cholinergic]] output of the central nervous system to the striatum and neocortex.<ref name="Goard">{{cite journal |last1=Goard |first1=M. |last2=Dan |first2=Y. |title=Basal forebrain activation enhances cortical coding of natural scenes |journal=Nature Neuroscience |date=October 4, 2009 |volume=12 |issue=11 |pages=1444–1449 |doi=10.1038/nn.2402|pmid=19801988 |pmc=3576925 }}</ref>

====Cerebellum====
[[File:Sobo 1909 623.png|thumb|upright=1.25|Human brain viewed from below, showing cerebellum and brainstem]]
{{Main|Biology:Cerebellum}}

The cerebellum is divided into an [[Biology:Anterior lobe of cerebellum|anterior lobe]], a [[Biology:Posterior lobe of cerebellum|posterior lobe]], and the [[Biology:Flocculonodular lobe|flocculonodular lobe]].{{sfn|Guyton & Hall|2011|p=699}} The anterior and posterior lobes are connected in the middle by the [[Biology:Cerebellar vermis|vermis]].{{sfn|Gray's Anatomy|2008|p=298}} Compared to the cerebral cortex, the cerebellum has a much thinner outer cortex that is narrowly furrowed into numerous curved transverse fissures.{{sfn|Gray's Anatomy|2008|p=298}}
Viewed from underneath between the two lobes is the third lobe the flocculonodular lobe.<ref>{{cite book |last1=Netter |first1=F. |title=Atlas of Human Anatomy Including Student Consult Interactive Ancillaries and Guides. |date=2014 |publisher=W B Saunders Co |location=Philadelphia, Penn. |isbn=978-1-4557-0418-7 |page=114 |edition=6th}}</ref> The cerebellum rests at the back of the cranial cavity, lying beneath the occipital lobes, and is separated from these by the cerebellar tentorium, a sheet of fibre.{{sfn|Gray's Anatomy|2008|p=297}}

It is connected to the brainstem by three pairs of [[Biology:Nerve tract|nerve tract]]s called cerebellar peduncles. The superior pair connects to the midbrain; the middle pair connects to the medulla, and the inferior pair connects to the pons.{{sfn|Gray's Anatomy|2008|p=298}} The cerebellum consists of an inner medulla of white matter and an outer cortex of richly folded grey matter.{{sfn|Gray's Anatomy|2008|p=297}} The cerebellum's anterior and posterior lobes appear to play a role in the coordination and smoothing of complex motor movements, and the flocculonodular lobe in the maintenance of balance{{sfn|Guyton & Hall|2011|pp=698–9}} although debate exists as to its cognitive, behavioural and motor functions.{{sfn|Squire|2013|pp=761–763}}

====Brainstem====
{{Main|Biology:Brainstem}}
The brainstem lies beneath the cerebrum and consists of the [[Biology:Midbrain|midbrain]], [[Biology:Pons|pons]] and medulla. It lies in the back part of the skull, resting on the part of the base known as the clivus, and ends at the foramen magnum, a large opening in the [[Biology:Occipital bone|occipital bone]]. The brainstem continues below this as the [[Biology:Spinal cord|spinal cord]],{{sfn|Gray's Anatomy|2008|p=275}} protected by the [[Biology:Vertebral column|vertebral column]].

Ten of the twelve pairs of cranial nerves{{efn|Specifically the oculomotor, [[Biology:Trochlear nerve|trochlear nerve]], [[Biology:Trigeminal nerve|trigeminal nerve]], [[Biology:Abducens nerve|abducens nerve]], [[Biology:Facial nerve|facial nerve]], [[Biology:Vestibulocochlear nerve|vestibulocochlear nerve]], [[Biology:Glossopharyngeal nerve|glossopharyngeal nerve]], [[Biology:Vagus nerve|vagus nerve]], [[Biology:Accessory nerve|accessory nerve]] and [[Biology:Hypoglossal nerve|hypoglossal nerve]]s.{{sfn|Gray's Anatomy|2008|p=275}}}} emerge directly from the brainstem.{{sfn|Gray's Anatomy|2008|p=275}} The brainstem also contains many cranial nerve nuclei and [[Biology:Nucleus (neuroanatomy)|nuclei]] of [[Biology:Nerve|peripheral nerves]], as well as nuclei involved in the regulation of many essential processes including [[Physics:Breathing|breathing]], control of eye movements and balance.{{sfn|Guyton & Hall|2011|p=691}}{{sfn|Gray's Anatomy|2008|p=275}} The [[Biology:Reticular formation|reticular formation]], a network of nuclei of ill-defined formation, is present within and along the length of the brainstem.{{sfn|Gray's Anatomy|2008|p=275}} Many [[Biology:Nerve tract|nerve tract]]s, which transmit information to and from the cerebral cortex to the rest of the body, pass through the brainstem.{{sfn|Gray's Anatomy|2008|p=275}}

===Microanatomy===
The human brain is primarily composed of [[Biology:Neuron|neuron]]s, glial cells, [[Biology:Neural stem cell|neural stem cell]]s, and [[Biology:Blood vessel|blood vessel]]s. Types of neuron include [[Biology:Interneuron|interneuron]]s, [[Biology:Pyramidal cell|pyramidal cell]]s including [[Biology:Betz cell|Betz cell]]s, motor neurons (upper and lower motor neurons), and cerebellar [[Biology:Purkinje cell|Purkinje cell]]s. Betz cells are the largest cells (by size of cell body) in the nervous system.{{sfn|Purves|2012|p=377}} The adult human brain is estimated to contain 86±8 billion neurons, with a roughly equal number (85±10 billion) of non-neuronal cells.<ref name=":1" /> Out of these neurons, 16 billion (19%) are located in the cerebral cortex, and 69 billion (80%) are in the cerebellum.<ref name="Bigos"/><ref name=":1">{{cite journal |last1=Azevedo |first1=F. |display-authors=0 |title=Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain |journal=The Journal of Comparative Neurology |date=April 10, 2009 |volume=513 |issue=5 |pages=532–541 |doi=10.1002/cne.21974 |quote=despite the widespread quotes that the human brain contains 100 billion neurons and ten times more glial cells, the absolute number of neurons and glial cells in the human brain remains unknown. Here we determine these numbers by using the isotropic fractionator and compare them with the expected values for a human-sized primate. We find that the adult male human brain contains on average 86.1 ± 8.1 billion NeuN-positive cells (“neurons”) and 84.6 ± 9.8 billion NeuN-negative (“nonneuronal”) cells. |pmid=19226510|s2cid=5200449 }}</ref>

Types of glial cell are [[Biology:Astrocyte|astrocyte]]s (including Bergmann glia), oligodendrocytes, ependymal cells (including tanycytes), [[Biology:Radial glial cell|radial glial cell]]s, [[Biology:Microglia|microglia]], and a subtype of oligodendrocyte progenitor cells. Astrocytes are the largest of the glial cells. They are [[Biology:Stellate cell|stellate cell]]s with many processes radiating from their [[Biology:Soma|cell bodies]]. Some of these processes end as perivascular end-feet on [[Biology:Capillary|capillary]] walls.<ref>{{Cite book |last1=Pavel |first1=Fiala |last2=Jiří |first2=Valenta |title=Central Nervous System |url=https://books.google.com/books?id=LPlSBAAAQBAJ&pg=PA79 |publisher=Karolinum Press |page=79 |date=January 1, 2013|isbn=978-80-246-2067-1 }}</ref> The [[Biology:Glia limitans|glia limitans]] of the cortex is made up of astrocyte foot processes that serve in part to contain the cells of the brain.<ref name="Anatomy and Ultrastructure"/>

[[Biology:Mast cell|Mast cell]]s are [[Biology:White blood cell|white blood cell]]s that interact in the [[Biology:Neuroimmune system|neuroimmune system]] in the brain.<ref name="Mast cell neuroimmmune system">{{cite journal | last1=Polyzoidis |first1=S. |last2=Koletsa |first2=T. |last3=Panagiotidou |first3=S. |last4=Ashkan |first4=K. |last5=Theoharides |first5=T.C. | title=Mast cells in meningiomas and brain inflammation | journal=Journal of Neuroinflammation | volume=12 | issue=1 | page=170 | year=2015 | pmid=26377554 | pmc=4573939 | doi=10.1186/s12974-015-0388-3 |doi-access=free }}</ref> Mast cells in the central nervous system are present in [[Biology:Mast cell#In the nervous system|a number of structures]] including the meninges;<ref name="Mast cell neuroimmmune system" /> they mediate neuroimmune responses in inflammatory conditions and help to maintain the blood–brain barrier, particularly in brain regions where the barrier is absent.<ref name="Mast cell neuroimmmune system" />{{sfn|Guyton & Hall|2011|pp=748–749}} Mast cells serve the same general functions in the body and central nervous system, such as effecting or regulating allergic responses, [[Biology:Innate immune system|innate]] and [[Biology:Adaptive immune system|adaptive immunity]], [[Medicine:Autoimmunity|autoimmunity]], and [[Medicine:Inflammation|inflammation]].<ref name="Mast cell neuroimmmune system" /> Mast cells serve as the main [[Biology:Effector cell|effector cell]] through which pathogens can affect the biochemical signaling that takes place between the gastrointestinal tract and the central nervous system.<ref name="pmid24833851">{{cite journal | last1=Budzyński |first1=J |last2=Kłopocka |first2=M. | title=Brain-gut axis in the pathogenesis of Helicobacter pylori infection | journal=World J. Gastroenterol. | volume=20 | issue=18 | pages=5212–25 | year=2014 | pmid=24833851 | pmc=4017036 | doi=10.3748/wjg.v20.i18.5212 |doi-access=free }}</ref><ref name="Microbiome-CNS-ENS">{{cite journal | last1=Carabotti |first1=M. |last2=Scirocco |first2=A. |last3=Maselli |first3=M.A. |last4=Severi |first4=C. | title=The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems | journal=Ann Gastroenterol | volume=28 | issue=2 | pages=203–209 | year=2015 | pmid=25830558 | pmc=4367209}}</ref>

Some 400 [[Biology:Gene|gene]]s are shown to be brain-specific. In all neurons, ELAVL3 is expressed, and in pyramidal neurons, NRGN and [[Biology:REEP2|REEP2]] are also expressed. GAD1 – essential for the biosynthesis of the neurotransmitter GABA – is expressed in interneurons. Proteins expressed in glial cells include astrocyte markers [[Biology:Glial fibrillary acidic protein|GFAP]] and [[Biology:S100B|S100B]] whereas [[Biology:Myelin basic protein|myelin basic protein]] and the transcription factor [[Biology:OLIG2|OLIG2]] are expressed in oligodendrocytes.<ref>{{Cite journal|last1=Sjöstedt|first1=Evelina|last2=Fagerberg|first2=Linn|last3=Hallström|first3=Björn M.|last4=Häggmark|first4=Anna|last5=Mitsios|first5=Nicholas|last6=Nilsson|first6=Peter|last7=Pontén|first7=Fredrik|last8=Hökfelt|first8=Tomas|last9=Uhlén|first9=Mathias|date=June 15, 2015|title=Defining the human brain proteome using transcriptomics and antibody-based profiling with a focus on the cerebral cortex|journal=PLOS ONE |volume=10|issue=6|page=e0130028 |doi=10.1371/journal.pone.0130028|pmid=26076492 |pmc=4468152|issn=1932-6203|bibcode=2015PLoSO..1030028S|doi-access=free}}</ref>

===Cerebrospinal fluid===
[[Image:Blausen 0216 CerebrospinalSystem.png|thumb|[[Biology:Cerebrospinal fluid|Cerebrospinal fluid]] circulates in spaces around and within the brain]]
{{Main|Biology:Cerebrospinal fluid}}
Cerebrospinal fluid is a clear, colourless [[Biology:Transcellular fluid|transcellular fluid]] that circulates around the brain in the subarachnoid space, in the [[Biology:Ventricular system|ventricular system]], and in the [[Biology:Central canal|central canal]] of the spinal cord. It also fills some gaps in the subarachnoid space, known as subarachnoid cisterns.{{sfn|Gray's Anatomy|2008|pp=242–244}} The four ventricles, two lateral, a third, and a fourth ventricle, all contain a choroid plexus that produces cerebrospinal fluid.{{sfn|Purves|2012|p=742}} The third ventricle lies in the midline and is connected to the lateral ventricles.{{sfn|Gray's Anatomy|2008|pp=242–244}} A single duct, the cerebral aqueduct between the pons and the cerebellum, connects the third ventricle to the fourth ventricle.{{sfn|Gray's Anatomy|2008|p=243}} Three separate openings, the middle and two lateral apertures, drain the cerebrospinal fluid from the fourth ventricle to the cisterna magna, one of the major cisterns. From here, cerebrospinal fluid circulates around the brain and spinal cord in the subarachnoid space, between the arachnoid mater and pia mater.{{sfn|Gray's Anatomy|2008|pp=242–244}}
At any one time, there is about 150mL of cerebrospinal fluid – most within the subarachnoid space. It is constantly being regenerated and absorbed, and is replaced about once every 5–6 hours.{{sfn|Gray's Anatomy|2008|pp=242–244}}

A [[Biology:Glymphatic system|glymphatic system]] has been described<ref name="lliff">{{cite journal |last1=Iliff |first1=JJ |last2=Nedergaard |first2=M |title=Is there a cerebral lymphatic system? |journal=Stroke |date=June 2013 |volume=44 |issue=6 Suppl 1 |pages=S93-5 |doi=10.1161/STROKEAHA.112.678698 |pmid=23709744|pmc=3699410 }}</ref><ref>{{cite web |last1=Gaillard |first1=F. |title=Glymphatic pathway |url=https://radiopaedia.org/articles/glymphatic-pathway |website=radiopaedia.org |url-status=live |archive-url=https://web.archive.org/web/20171030002906/https://radiopaedia.org/articles/glymphatic-pathway |archive-date=October 30, 2017}}</ref><ref name="Glymphatic system and brain waste clearance 2017 review" /> as the lymphatic drainage system of the brain. The brain-wide glymphatic pathway includes drainage routes from the cerebrospinal fluid, and from the [[Biology:Meningeal lymphatic vessels|meningeal lymphatic vessels]] that are associated with the dural sinuses, and run alongside the cerebral blood vessels.<ref name="D-O">{{cite journal|last1=Dissing-Olesen|first1=L.|last2=Hong|first2=S. |last3=Stevens|first3=B. |title=New brain lymphatic vessels drain old concepts |journal=eBioMedicine |date=August 2015|volume=2|issue=8|pages=776–7|doi=10.1016/j.ebiom.2015.08.019|pmid=26425672|pmc=4563157}}</ref><ref name="Sun">{{cite journal |last1=Sun |first1=BL |last2=Wang |first2=LH |last3=Yang |first3=T |last4=Sun |first4=JY |last5=Mao |first5=LL |last6=Yang |first6=MF |last7=Yuan |first7=H |last8=Colvin |first8=RA |last9=Yang |first9=XY |title=Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases. |journal=Progress in Neurobiology |date=April 2018 |volume=163–164 |pages=118–143 |doi=10.1016/j.pneurobio.2017.08.007 |pmid=28903061|s2cid=6290040 }}</ref> The pathway drains [[Biology:Interstitial fluid|interstitial fluid]] from the tissue of the brain.<ref name="Sun"/>

===Blood supply===
{{Main|Biology:Cerebral circulation}}
[[File:Circle of Willis en.svg|thumb|upright|Two circulations joining at the circle of Willis (inferior view)]]
[[File:Gray769-en.svg|thumb|Diagram showing features of cerebral [[Medicine:Meninges|outer membranes]] and supply of blood vessels]]
<!-- Arteries -->The internal carotid arteries supply [[Biology:Blood#Oxygen transport|oxygenated blood]] to the front of the brain and the vertebral arteries supply blood to the back of the brain.{{sfn|Gray's Anatomy|2008|p=247}} These two circulations [[Biology:Anastomosis|join]] in the circle of Willis, a ring of connected arteries that lies in the interpeduncular cistern between the midbrain and pons.{{sfn|Gray's Anatomy|2008|pp=251-2}}

The internal carotid arteries are branches of the common carotid arteries. They enter the cranium through the [[Medicine:Carotid canal|carotid canal]], travel through the [[Medicine:Cavernous sinus|cavernous sinus]] and enter the subarachnoid space.{{sfn|Gray's Anatomy|2008|p=250}} They then enter the circle of Willis, with two branches, the anterior cerebral arteries emerging. These branches travel forward and then upward along the [[Biology:Longitudinal fissure|longitudinal fissure]], and supply the front and midline parts of the brain.{{sfn|Gray's Anatomy|2008|p=248}} One or more small anterior communicating arteries join the two anterior cerebral arteries shortly after they emerge as branches.{{sfn|Gray's Anatomy|2008|p=248}} The internal carotid arteries continue forward as the middle cerebral arteries. They travel sideways along the sphenoid bone of the [[Biology:Orbit (anatomy)|eye socket]], then upwards through the insula cortex, where final branches arise. The middle cerebral arteries send branches along their length.{{sfn|Gray's Anatomy|2008|p=250}}

The vertebral arteries emerge as branches of the left and right subclavian arteries. They travel upward through [[Biology:Vertebra#Cervical vertebrae|transverse foramina]] which are spaces in the cervical vertebrae. Each side enters the cranial cavity through the foramen magnum along the corresponding side of the medulla.{{sfn|Gray's Anatomy|2008|p=250}} They give off one of the three cerebellar branches. The vertebral arteries join in front of the middle part of the medulla to form the larger basilar artery, which sends multiple branches to supply the medulla and pons, and the two other anterior and superior cerebellar branches.{{sfn|Gray's Anatomy|2008|p=251}} Finally, the basilar artery divides into two posterior cerebral arteries. These travel outwards, around the superior cerebellar peduncles, and along the top of the cerebellar tentorium, where it sends branches to supply the temporal and occipital lobes.{{sfn|Gray's Anatomy|2008|p=251}} Each posterior cerebral artery sends a small posterior communicating artery to join with the internal carotid arteries.

====Blood drainage====
<!--Veins-->
Cerebral veins drain [[Biology:Blood#Oxygen transport|deoxygenated blood]] from the brain. The brain has two main networks of [[Medicine:Vein|vein]]s: an exterior or superficial network, on the surface of the cerebrum that has three branches, and an interior network. These two networks communicate via [[Biology:Anastomosis|anastomosing]] (joining) veins.{{sfn|Gray's Anatomy|2008|pp=254-6}} The veins of the brain drain into larger cavities of the dural venous sinuses usually situated between the dura mater and the covering of the skull.{{sfn|Elsevier's|2007|pp=311–4}} Blood from the cerebellum and midbrain drains into the great cerebral vein. Blood from the medulla and pons of the brainstem have a variable pattern of drainage, either into the spinal veins or into adjacent cerebral veins.{{sfn|Gray's Anatomy|2008|pp=254-6}}

The blood in the [[Biology:Anatomical terms of location#deep|deep]] part of the brain drains, through a venous plexus into the [[Medicine:Cavernous sinus|cavernous sinus]] at the front, and the superior and inferior petrosal sinuses at the sides, and the inferior sagittal sinus at the back.{{sfn|Elsevier's|2007|pp=311–4}} Blood drains from the outer brain into the large superior sagittal sinus, which rests in the midline on top of the brain. Blood from here joins with blood from the straight sinus at the confluence of sinuses.{{sfn|Elsevier's|2007|pp=311–4}}

Blood from here drains into the left and right transverse sinuses.{{sfn|Elsevier's|2007|pp=311–4}} These then drain into the sigmoid sinuses, which receive blood from the cavernous sinus and superior and inferior petrosal sinuses. The sigmoid drains into the large [[Medicine:Internal jugular vein|internal jugular vein]]s.{{sfn|Elsevier's|2007|pp=311–4}}{{sfn|Gray's Anatomy|2008|pp=254-6}}

====The blood–brain barrier====
The larger arteries throughout the brain supply blood to smaller capillaries. These smallest of [[Biology:Blood vessel|blood vessel]]s in the brain, are lined with cells joined by [[Biology:Tight junction|tight junction]]s and so fluids do not seep in or leak out to the same degree as they do in other capillaries; this creates the [[Biology:Blood–brain barrier|blood–brain barrier]].{{sfn|Guyton & Hall|2011|pp=748–749}} [[Biology:Pericyte|Pericyte]]s play a major role in the formation of the tight junctions.<ref name="Daneman">{{cite journal |last1=Daneman |first1=R. |last2=Zhou |first2=L. |last3=Kebede |first3=A.A. |last4=Barres |first4=B.A. |title=Pericytes are required for blood-brain barrier integrity during embryogenesis |journal=Nature |date=November 25, 2010 |volume=468 |issue=7323 |pages=562–6 |pmid=20944625 |doi=10.1038/nature09513 |pmc=3241506|bibcode=2010Natur.468..562D }}</ref> The barrier is less permeable to larger molecules, but is still permeable to water, carbon dioxide, oxygen, and most fat-soluble substances (including anaesthetics and alcohol).{{sfn|Guyton & Hall|2011|pp=748–749}} The blood-brain barrier is not present in the circumventricular organs{{Em dash}}which are structures in the brain that may need to respond to changes in body fluids{{Em dash}}such as the [[Biology:Pineal gland|pineal gland]], area postrema, and some areas of the [[Biology:Hypothalamus|hypothalamus]].{{sfn|Guyton & Hall|2011|pp=748–749}} There is a similar blood–cerebrospinal fluid barrier, which serves the same purpose as the blood–brain barrier, but facilitates the transport of different substances into the brain due to the distinct structural characteristics between the two barrier systems.{{sfn|Guyton & Hall|2011|pp=748–749}}<ref name="BCSF">{{cite book |last1=Laterra |first1=J. |last2=Keep |first2=R. |last3=Betz |first3=L.A. |title=Basic neurochemistry: molecular, cellular and medical aspects |date=1999 |publisher=Lippincott-Raven |location=Philadelphia |edition=6th |section-url=https://www.ncbi.nlm.nih.gov/books/NBK27998/ |section=Blood–cerebrospinal fluid barrier |display-authors=0}}</ref>

==Development==
{{Main |Biology:Development of the nervous system in humans}}
{{Further|Biology:Development of the human brain}}
[[File:Embryonic Development CNS.png|thumb|upright=1.25|Neurulation and neural crest cells]]
[[File:1302 Brain Vesicle DevN.jpg|thumb|upright=1.25|alt= Simple drawing of the lateral view of the three primary vesicle stage of the three to four week old embryo shown in different colors, and the five secondary vesicle stage of the five week old embryo shown in different colors and a lateral view of this |Primary and secondary vesicle stages of development in the early embryo to the fifth week]]
[[File:6 week embryo brain.jpg|thumb|alt=Very simple drawing of the front end of a human embryo, showing each vesicle of the developing brain in a different color. |Brain of a human embryo in the sixth week of development]]

At the beginning of the third week of [[Biology:Human embryonic development|development]], the [[Biology:Embryo|embryo]]nic [[Biology:Ectoderm|ectoderm]] forms a thickened strip called the neural plate.<ref name="Sadler">{{cite book |last1=Sadler |first1=T. |title=Langman's medical embryology |date=2010 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-9069-7 |page=293 |edition=11th}}</ref> By the fourth week of development the neural plate has widened to give a broad [[Biology:Cephalization|cephalic]] end, a less broad middle part and a narrow caudal end. These swellings are known as the primary brain vesicles and represent the beginnings of the [[Biology:Forebrain|forebrain]] (prosencephalon), [[Biology:Midbrain|midbrain]] (mesencephalon), and hindbrain (rhombencephalon).{{sfn|Larsen|2001|p=419}}<ref>{{Cite journal |last1=Zhou |first1=Yi |last2=Song |first2=Hongjun |last3=Ming |first3=Guo-Li |date=2023-07-28 |title=Genetics of human brain development |url=https://pubmed.ncbi.nlm.nih.gov/37507490 |journal=Nature Reviews. Genetics |volume=25 |issue=1 |pages=26–45 |doi=10.1038/s41576-023-00626-5 |issn=1471-0064 |pmid=37507490|s2cid=260286574 }}</ref>

[[Biology:Neural crest|Neural crest cells]] (derived from the ectoderm) populate the lateral edges of the plate at the neural folds. In the fourth week{{Em dash}}during the neurulation stage{{Em dash}}the neural folds close to form the [[Biology:Neural tube|neural tube]], bringing together the neural crest cells at the [[Biology:Neural crest|neural crest]].{{sfn|Larsen|2001|pp=85–88}} The neural crest runs the length of the tube with cranial neural crest cells at the cephalic end and caudal neural crest cells at the tail. Cells detach from the crest and [[Biology:Cell migration|migrate]] in a craniocaudal (head to tail) wave inside the tube.{{sfn|Larsen|2001|pp=85–88}} Cells at the cephalic end give rise to the brain, and cells at the caudal end give rise to the spinal cord.{{sfn|Purves|2012|pp=480–482}}

The tube [[Biology:Flexure (embryology)|flexes]] as it grows, forming the crescent-shaped cerebral hemispheres at the head. The cerebral hemispheres first appear on day 32.{{sfn|Larsen|2001|pp=445–446}}
Early in the fourth week, the cephalic part bends sharply forward in a cephalic flexure.{{sfn|Larsen|2001|pp=85–88}} This flexed part becomes the forebrain (prosencephalon); the adjoining curving part becomes the midbrain (mesencephalon) and the part caudal to the flexure becomes the hindbrain (rhombencephalon). These areas are formed as swellings known as the three primary brain vesicles. In the fifth week of development five secondary brain vesicles have formed.<ref>{{Cite web|title = OpenStax CNX|url = http://cnx.org/contents/b037bde2-ea37-43a5-9102-8d4fcbc623d1@3/The_Embryologic_Perspective|website = cnx.org|access-date = May 5, 2015|url-status = live|archive-url = https://web.archive.org/web/20150505054856/http://cnx.org/contents/b037bde2-ea37-43a5-9102-8d4fcbc623d1@3/The_Embryologic_Perspective|archive-date = May 5, 2015|df = mdy-all}}</ref> The forebrain separates into two vesicles – an anterior telencephalon and a posterior [[Biology:Diencephalon|diencephalon]]. The telencephalon gives rise to the cerebral cortex, basal ganglia, and related structures. The diencephalon gives rise to the thalamus and hypothalamus. The hindbrain also splits into two areas – the [[Biology:Metencephalon|metencephalon]] and the [[Biology:Myelencephalon|myelencephalon]]. The metencephalon gives rise to the cerebellum and pons. The myelencephalon gives rise to the medulla oblongata.{{sfn|Larsen|2001|pp=85–87}} Also during the fifth week, the brain divides into [[Biology:Segmentation|repeating segments]] called neuromeres.{{sfn|Larsen|2001|p=419}}{{sfn|Purves|2012|pp=481–484}} In the hindbrain these are known as rhombomeres.<ref name=Neuro>{{cite book |editor1-first=Dale |editor1-last=Purves |editor2-first=George J |editor2-last=Augustine |editor3-first=David |editor3-last=Fitzpatrick |editor4-first=Lawrence C |editor4-last=Katz |editor5-first=Anthony-Samuel |editor5-last=LaMantia |editor6-first=James O |editor6-last=McNamara |editor7-first=S Mark |editor7-last=Williams |year=2001 |chapter=Rhombomeres |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK10954/box/A1478/ |title=Neuroscience |publisher=Palgrave Macmillan |edition=2nd |isbn=978-0-87893-742-4}}</ref>

A characteristic of the brain is the cortical folding known as [[Biology:Gyrification|gyrification]]. For just over five months of [[Biology:Prenatal development|prenatal development]] the cortex is smooth. By the gestational age of 24 weeks, the wrinkled morphology showing the fissures that begin to mark out the lobes of the brain is evident.<ref name="Chen">{{cite book |url=https://books.google.com/books?id=94aPR_Oh40oC&pg=PA188 |title=Mechanical Self-Assembly: Science and Applications |publisher=Springer Science & Business Media |year=2012 |isbn=978-1-4614-4562-3 |pages=188–189 |last=Chen |first=X.}}</ref> Why the cortex wrinkles and folds is not well-understood, but gyrification has been linked to intelligence and [[Medicine:Neurological disorder|neurological disorder]]s, and a [[Biology:Gyrification#Theories on causality in gyrification|number of gyrification theories]] have been proposed.<ref name="Chen"/> These theories include those based on [[Biology:Gyrification#Mechanical buckling|mechanical buckling]],<ref name="Ronan">{{cite journal |last1=Ronan |first1=L |last2=Voets |first2=N |last3=Rua |first3=C |last4=Alexander-Bloch |first4=A |last5=Hough |first5=M |last6=Mackay |first6=C |last7=Crow |first7=TJ |last8=James |first8=A |last9=Giedd |first9=JN |last10=Fletcher |first10=PC |title=Differential tangential expansion as a mechanism for cortical gyrification. |journal=Cerebral Cortex |date=August 2014 |volume=24 |issue=8 |pages=2219–28 |doi=10.1093/cercor/bht082 |pmid=23542881|pmc=4089386 }}</ref><ref name="Ackerman">{{cite book |last1=Ackerman |first1=S. |title=Discovering the brain |url=https://archive.org/details/discoveringbrain00acke |url-access=registration |date=1992 |publisher=National Academy Press |location=Washington, D.C. |isbn=978-0-309-04529-2 |pages=[https://archive.org/details/discoveringbrain00acke/page/22 22–25]}}</ref> [[Biology:Gyrification#Axonal tension|axonal tension]],<ref name="Van Essen">{{cite journal |last1=Van Essen |first1=DC |title=A tension-based theory of morphogenesis and compact wiring in the central nervous system. |journal=Nature |date=January 23, 1997 |volume=385 |issue=6614 |pages=313–8 |doi=10.1038/385313a0 |pmid=9002514|bibcode=1997Natur.385..313E |s2cid=4355025 }}</ref> and [[Biology:Gyrification#Differential tangential expansion|differential tangential expansion]].<ref name="Ronan"/> What is clear is that gyrification is not a random process, but rather a complex developmentally predetermined process which generates patterns of folds that are consistent between individuals and most species.<ref name="Ronan"/><ref name="Borrell">{{cite journal |last1=Borrell |first1=V |title=How Cells Fold the Cerebral Cortex. |journal=The Journal of Neuroscience |date=24 January 2018 |volume=38 |issue=4 |pages=776–783 |doi=10.1523/JNEUROSCI.1106-17.2017 |pmid=29367288|pmc=6596235 }}</ref>

The first groove to appear in the fourth month is the lateral cerebral fossa.{{sfn|Larsen|2001|pp=445–446}} The expanding caudal end of the hemisphere has to curve over in a forward direction to fit into the restricted space. This covers the fossa and turns it into a much deeper ridge known as the [[Biology:Lateral sulcus|lateral sulcus]] and this marks out the temporal lobe.{{sfn|Larsen|2001|pp=445–446}} By the sixth month other sulci have formed that demarcate the frontal, parietal, and occipital lobes.{{sfn|Larsen|2001|pp=445–446}} A gene present in the human genome ([[Biology:ARHGAP11B|ARHGAP11B]]) may play a major role in gyrification and encephalisation.<ref>{{cite journal |last1=Florio |first1=M.|display-authors=0 |title=Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion |journal=Science |date=March 27, 2015 |volume=347 |issue=6229 |pages=1465–70 |pmid=25721503 |doi=10.1126/science.aaa1975|bibcode=2015Sci...347.1465F|s2cid=34506325|doi-access=free }}</ref>
{{Gallery
 | title=
 | width=200
 | height=180
 |File:Gray651.png |Brain of human embryo at 4.5 weeks, showing interior of forebrain
 |File:Gray653.png |Brain interior at 5 weeks
 |File:Gray654.png |Brain viewed at midline at 3 months
}}

==Function==
[[File:Blausen 0103 Brain Sensory&Motor.png|thumb|upright=1.4|Motor and sensory regions of the brain]]

===Motor control===
The frontal lobe is involved in reasoning, motor control, emotion, and language. It contains the [[Biology:Motor cortex|motor cortex]], which is involved in planning and coordinating movement; the [[Biology:Prefrontal cortex|prefrontal cortex]], which is responsible for higher-level cognitive functioning; and Broca’s area, which is essential for language production.<ref>{{Cite web|url=https://courses.lumenlearning.com/wmopen-psychology/chapter/outcome-parts-of-the-brain/|title=Parts of the Brain {{!}} Introduction to Psychology|website=courses.lumenlearning.com|access-date=2019-09-20}}</ref> The [[Biology:Motor system|motor system]] of the brain is responsible for the [[Engineering:Motor control|generation and control]] of movement.{{sfn|Guyton & Hall|2011|p=685}} Generated movements pass from the brain through nerves to motor neurons in the body, which control the action of [[Biology:Muscle|muscle]]s. The corticospinal tract carries movements from the brain, through the [[Biology:Spinal cord|spinal cord]], to the torso and limbs.{{sfn|Guyton & Hall|2011|p=687}} The cranial nerves carry movements related to the eyes, mouth and face.

Gross movement – such as [[Biology:Animal locomotion|locomotion]] and the movement of arms and legs – is generated in the [[Biology:Motor cortex|motor cortex]], divided into three parts: the [[Biology:Primary motor cortex|primary motor cortex]], found in the [[Biology:Precentral gyrus|precentral gyrus]] and has sections dedicated to the movement of different body parts. These movements are supported and regulated by two other areas, lying anterior to the primary motor cortex: the premotor area and the [[Biology:Supplementary motor area|supplementary motor area]].{{sfn|Guyton & Hall|2011|p=686}} The hands and mouth have a much larger area dedicated to them than other body parts, allowing finer movement; this has been visualised in a [[Cortical homunculus#Types|motor homunculus]].{{sfn|Guyton & Hall|2011|p=686}} Impulses generated from the motor cortex travel along the corticospinal tract along the front of the medulla and cross over (decussate) at the medullary pyramids. These then travel down the [[Biology:Spinal cord|spinal cord]], with most connecting to [[Biology:Spinal interneuron|interneuron]]s, in turn connecting to lower motor neurons within the [[Biology:Grey matter|grey matter]] that then transmit the impulse to move to muscles themselves.{{sfn|Guyton & Hall|2011|p=687}} The cerebellum and [[Biology:Basal ganglia|basal ganglia]], play a role in fine, complex and coordinated muscle movements.{{sfn|Guyton & Hall|2011|pp=698, 708}} Connections between the cortex and the basal ganglia control muscle tone, posture and movement initiation, and are referred to as the [[Biology:Extrapyramidal system|extrapyramidal system]].{{sfn|Davidson's|2010|p=1139}}

===Sensory===
[[File:1604 Types of Cortical Areas-02.jpg|thumb|upright=1.3|Cortical areas]]
[[File:Gray722.png|thumb|upright=0.9|Routing of neural signals from the two eyes to the brain]]
The [[Biology:Sensory nervous system|sensory nervous system]] is involved with the reception and processing of [[Philosophy:Sense|sensory information]]. This information is received through the cranial nerves, through tracts in the spinal cord, and directly at centres of the brain exposed to the blood.<ref name="Hellier">{{cite book |author=Hellier, J. |title=The Brain, the Nervous System, and Their Diseases [3 volumes] |publisher=[[Company:ABC-CLIO|ABC-CLIO]] |year=2014 |pages=300–303 |isbn=978-1-61069-338-7 |url=https://books.google.com/books?id=SDi2BQAAQBAJ&pg=PA300}}</ref> The brain also receives and interprets information from the special senses of [[Philosophy:Visual perception|vision]], [[Biology:Olfaction|smell]], [[Physics:Hearing|hearing]], and [[Biology:Taste|taste]]. [[Biology:Sensory-motor coupling|Mixed motor and sensory signals]] are also integrated.<ref name="Hellier"/>

From the skin, the brain receives information about fine touch, [[Physics:Pressure|pressure]], [[Medicine:Pain|pain]], [[Vibration|vibration]] and [[Physics:Temperature|temperature]]. From the joints, the brain receives information about [[Biology:Proprioception|joint position]].{{sfn|Guyton & Hall|2011|pp=571–576}} The [[Biology:Sensory cortex|sensory cortex]] is found just near the motor cortex, and, like the motor cortex, has areas related to sensation from different body parts. Sensation collected by a sensory receptor on the skin is changed to a nerve signal, that is passed up a series of neurons through tracts in the spinal cord. The [[Biology:Dorsal column–medial lemniscus pathway|dorsal column–medial lemniscus pathway]] contains information about fine touch, vibration and position of joints. The pathway fibres travel up the back part of the spinal cord to the back part of the medulla, where they connect with [[Biology:Dorsal column–medial lemniscus pathway#Second-order neurons|second-order neurons]] that immediately [[Biology:Decussation|send fibres across the midline]]. These fibres then travel upwards into the [[Biology:Ventrobasal complex|ventrobasal complex]] in the thalamus where they connect with [[Biology:Dorsal column–medial lemniscus pathway#Third-order neurons|third-order neurons]] which send fibres up to the sensory cortex.{{sfn|Guyton & Hall|2011|pp=571–576}} The [[Biology:Spinothalamic tract|spinothalamic tract]] carries information about pain, temperature, and gross touch. The pathway fibres travel up the spinal cord and connect with second-order neurons in the [[Biology:Reticular formation|reticular formation]] of the brainstem for pain and temperature, and also terminate at the ventrobasal complex of the thalamus for gross touch.{{sfn|Guyton & Hall|2011|pp=573–574}}

[[Philosophy:Visual perception|Vision]] is generated by light that hits the [[Biology:Retina|retina]] of the eye. [[Biology:Photoreceptor cell|Photoreceptors]] in the retina [[Biology:Visual phototransduction|transduce]] the sensory stimulus of [[Physics:Electromagnetic radiation|light]] into an electrical [[Biology:Action potential|nerve signal]] that is sent to the [[Biology:Visual cortex|visual cortex]] in the occipital lobe. Visual signals leave the retinas through the optic nerves.
Optic nerve fibres from the retinas' nasal halves [[Biology:Optic chiasm|cross to the opposite sides]] joining the fibres from the temporal halves of the opposite retinas to form the optic tracts.
The arrangements of the eyes' optics and the visual pathways mean vision from the left [[Biology:Visual field|visual field]] is received by the right half of each retina, is processed by the right visual cortex, and vice versa. 
The optic tract fibres reach the brain at the [[Biology:Lateral geniculate nucleus|lateral geniculate nucleus]], and travel through the [[Biology:Optic radiation|optic radiation]] to reach the visual cortex.{{sfn|Guyton & Hall|2011|pp=623-631}}

[[Physics:Hearing|Hearing]] and balance are both generated in the inner ear. Sound results in vibrations of the [[Medicine:Ossicles|ossicles]] which continue finally to [[Biology:Hair cell|the hearing organ]], and change in balance results in movement of [[Biology:Vestibular system|liquids within the inner ear]]. This creates a nerve signal that passes through the [[Biology:Vestibulocochlear nerve|vestibulocochlear nerve]]. From here, it passes through to the cochlear nuclei, the superior olivary nucleus, the medial geniculate nucleus, and finally the auditory radiation to the [[Biology:Auditory cortex|auditory cortex]].{{sfn|Guyton & Hall|2011|pp=739–740}}

The sense of [[Biology:Olfaction|smell]] is generated by [[Biology:Olfactory receptor neuron|receptor cells]] in the epithelium of the olfactory mucosa in the nasal cavity. This information passes via the [[Biology:Olfactory nerve|olfactory nerve]] which goes into the skull through a relatively permeable part. This nerve transmits to the neural circuitry of the [[Biology:Olfactory bulb|olfactory bulb]] from where information is passed to the olfactory cortex.{{sfn|Pocock|2006|pp=138–139}}{{sfn|Squire|2013|pp=525–526}}
[[Biology:Taste|Taste]] is generated from [[Biology:Taste receptor|receptors on the tongue]] and passed along the [[Biology:Facial nerve|facial]] and [[Biology:Glossopharyngeal nerve|glossopharyngeal nerve]]s into the solitary nucleus in the brainstem. Some taste information is also passed from the pharynx into this area via the [[Biology:Vagus nerve|vagus nerve]]. Information is then passed from here through the thalamus into the [[Biology:Gustatory cortex|gustatory cortex]].{{sfn|Guyton & Hall|2011|pp=647–648}}

===Regulation===
Autonomic functions of the brain include the regulation, or [[Biology:Neuroscience of rhythm|rhythmic control]] of the [[Heart rate|heart rate]] and [[Respiratory rate|rate of breathing]], and maintaining [[Homeostasis|homeostasis]].

[[Physics:Blood pressure|Blood pressure]] and [[Heart rate|heart rate]] are influenced by the vasomotor centre of the medulla, which causes arteries and veins to be somewhat constricted at rest. It does this by influencing the sympathetic and parasympathetic nervous systems via the [[Biology:Vagus nerve|vagus nerve]].{{sfn|Guyton & Hall|2011|pp=202–203}} Information about blood pressure is generated by [[Biology:Baroreceptor|baroreceptor]]s in [[Biology:Aortic body|aortic bodies]] in the aortic arch, and passed to the brain along the afferent fibres of the vagus nerve. Information about the pressure changes in the carotid sinus comes from [[Biology:Carotid body|carotid bodies]] located near the carotid artery and this is passed via a nerve joining with the [[Biology:Glossopharyngeal nerve|glossopharyngeal nerve]]. This information travels up to the solitary nucleus in the medulla. Signals from here influence the vasomotor centre to adjust vein and artery constriction accordingly.{{sfn|Guyton & Hall|2011|pp=205–208}}

The brain controls the [[Respiratory rate|rate of breathing]], mainly by respiratory centres in the medulla and pons.{{sfn|Guyton & Hall|2011|pp=505–509}} The respiratory centres control [[Biology:Respiration (physiology)|respiration]], by generating motor signals that are passed down the spinal cord, along the phrenic nerve to the diaphragm and other [[Biology:Muscles of respiration|muscles of respiration]]. This is a mixed nerve that carries sensory information back to the centres. There are four respiratory centres, three with a more clearly defined function, and an apneustic centre with a less clear function. In the medulla a dorsal respiratory group causes the desire to [[Biology:Inhalation|breathe in]] and receives sensory information directly from the body. Also in the medulla, the ventral respiratory group influences [[Biology:Exhalation|breathing out]] during exertion. In the pons the pneumotaxic centre influences the duration of each breath,{{sfn|Guyton & Hall|2011|pp=505–509}} and the apneustic centre seems to have an influence on inhalation. The respiratory centres directly senses blood [[Chemistry:Carbon dioxide|carbon dioxide]] and [[Chemistry:PH|pH]]. Information about blood [[Chemistry:Oxygen|oxygen]], [[Chemistry:Carbon dioxide|carbon dioxide]] and pH levels are also sensed on the walls of arteries in the peripheral chemoreceptors of the aortic and carotid bodies. This information is passed via the vagus and glossopharyngeal nerves to the respiratory centres. High carbon dioxide, an acidic pH, or low oxygen stimulate the respiratory centres.{{sfn|Guyton & Hall|2011|pp=505–509}} The desire to breathe in is also affected by pulmonary stretch receptors in the lungs which, when activated, prevent the lungs from overinflating by transmitting information to the respiratory centres via the vagus nerve.{{sfn|Guyton & Hall|2011|pp=505–509}}

The [[Biology:Hypothalamus|hypothalamus]] in the [[Biology:Diencephalon|diencephalon]], is involved in regulating many functions of the body. Functions include neuroendocrine regulation, regulation of the [[Biology:Circadian rhythm|circadian rhythm]], control of the autonomic nervous system, and the regulation of fluid, and food intake. The circadian rhythm is controlled by two main cell groups in the hypothalamus. The anterior hypothalamus includes the [[Biology:Suprachiasmatic nucleus|suprachiasmatic nucleus]] and the ventrolateral preoptic nucleus which through gene expression cycles, generates a roughly 24 hour [[Circadian clock|circadian clock]]. In the [[Circadian clock|circadian day]] an [[Biology:Ultradian rhythm|ultradian rhythm]] takes control of the sleeping pattern. [[Biology:Sleep|Sleep]] is an essential requirement for the body and brain and allows the closing down and resting of the body's systems. There are also findings that suggest that the daily build-up of toxins in the brain are removed during sleep.<ref name="sleep">{{cite web |title=Brain Basics: Understanding Sleep {{!}} National Institute of Neurological Disorders and Stroke |url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understanding-Sleep |website=www.ninds.nih.gov |url-status=live |archive-url=https://web.archive.org/web/20171222044016/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understanding-Sleep |archive-date=December 22, 2017  }}</ref> Whilst awake the brain consumes a fifth of the body's total energy needs. [[Biology:Neuroscience of sleep|Sleep]] necessarily reduces this use and gives time for the restoration of energy-giving [[Chemistry:Adenosine triphosphate|ATP]]. The effects of [[Medicine:Sleep deprivation|sleep deprivation]] show the absolute need for sleep.{{sfn|Guyton & Hall|2011|p=723}}

The [[Biology:Lateral hypothalamus|lateral hypothalamus]] contains [[Biology:Orexin|orexin]]ergic neurons that control [[Medicine:Appetite|appetite]] and [[Medicine:Arousal|arousal]] through their projections to the ascending reticular activating system.<ref name=Davis>{{ cite book | chapter=24. Orexigenic Hypothalamic Peptides Behavior and Feeding – 24.5 Orexin | chapter-url=https://books.google.com/books?id=KuAEPOPbW6MC&pg=PA361 | pages=361–362 |last1=Davis |first1=J.F. |last2=Choi |first2=D.L. |last3=Benoit |first3=S.C. | title=Handbook of Behavior, Food and Nutrition |editor1-last=Preedy |editor1-first= V.R. |editor2-last=Watson |editor2-first=R.R. |editor3-last=Martin |editor3-first=C.R. | publisher=Springer | year=2011 | isbn=978-0-387-92271-3 }}</ref>{{sfn|Squire|2013|p=800}} The hypothalamus controls the [[Medicine:Pituitary gland|pituitary gland]] through the release of peptides such as [[Chemistry:Oxytocin|oxytocin]], and [[Biology:Vasopressin|vasopressin]], as well as [[Biology:Dopamine|dopamine]] into the median eminence. Through the autonomic projections, the hypothalamus is involved in regulating functions such as blood pressure, heart rate, breathing, sweating, and other homeostatic mechanisms.{{sfn|Squire|2013|p=803}} The hypothalamus also plays a role in thermal regulation, and when stimulated by the immune system, is capable of generating a [[Medicine:Fever|fever]]. The hypothalamus is influenced by the kidneys: when blood pressure falls, the [[Biology:Renin|renin]] released by the kidneys stimulates a need to drink. The hypothalamus also regulates food intake through autonomic signals, and hormone release by the digestive system.{{sfn|Squire|2013|p=805}}

===Language===
[[File:1605_Brocas_and_Wernickes_Areas-02.jpg|thumb|Broca's area and Wernicke's area are linked by the arcuate fasciculus.]]
{{Main |Biology:Language processing in the brain}}

While language functions were traditionally thought to be localised to [[Biology:Wernicke's area|Wernicke's area]] and [[Biology:Broca's area|Broca's area]],{{sfn|Guyton & Hall|2011|pp=720-2}} it is now mostly accepted that a wider network of [[Biology:Cortex (anatomy)|cortical]] regions contributes to language functions.<ref>{{cite journal |last1=Poeppel |first1=D. |last2=Emmorey |first2=K. |last3=Hickok |first3=G. |last4=Pylkkänen |first4=L.|author4-link=Liina Pylkkänen |title=Towards a new neurobiology of language |journal=The Journal of Neuroscience |date=October 10, 2012 |volume=32 |issue=41 |pages=14125–14131 |doi=10.1523/JNEUROSCI.3244-12.2012 |pmid=23055482 |pmc=3495005}}</ref><ref>{{cite journal |last1=Hickok |first1=G |title=The functional neuroanatomy of language |journal=Physics of Life Reviews |date=September 2009 |volume=6 |issue=3 |pages=121–143 |doi=10.1016/j.plrev.2009.06.001|pmid=20161054 |pmc=2747108 |bibcode=2009PhLRv...6..121H }}</ref><ref>{{cite journal | last1=Fedorenko | first1=E. | last2=Kanwisher | first2=N. | journal=Language and Linguistics Compass | volume=3 | issue=4 | title=Neuroimaging of language: why hasn't a clearer picture emerged? | pages=839–865 | doi=10.1111/j.1749-818x.2009.00143.x | year=2009 | s2cid=2833893 | df=mdy-all | doi-access=free }}</ref>

The study on how language is represented, processed, and [[Social:Language acquisition|acquired]] by the brain is called neurolinguistics, which is a large multidisciplinary field drawing from [[Cognitive neuroscience|cognitive neuroscience]], [[Philosophy:Cognitive linguistics|cognitive linguistics]], and [[Social:Psycholinguistics|psycholinguistics]].<ref>{{Cite book |title=Language intervention strategies in aphasia and related neurogenic communication disorders |last=Damasio |first=H. |date=2001 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2133-2 |editor-last=Chapey |editor-first=Roberta |edition=4th |pages=18–36 |chapter=Neural basis of language disorders |oclc=45952164}}</ref>

===Lateralisation===
{{Main |Biology:Lateralization of brain function}}
{{Further |Biology:Functional specialization (brain)}}
The cerebrum has a [[Biology:Contralateral brain|contralateral organisation]] with each hemisphere of the brain interacting primarily with one half of the body: the left side of the brain interacts with the right side of the body, and vice versa. This is theorized to be caused by a developmental axial twist.<ref name="Lussanet2012">{{cite journal | first1=M.H.E. | last1=de Lussanet | first2=J.W.M. | last2=Osse | year=2012 | title=An ancestral axial twist explains the contralateral forebain and the optic chiasm in vertebrates | journal=Animal Biology | volume=62 | issue=2 | pages=193–216 | doi=10.1163/157075611X617102 | arxiv=1003.1872 | s2cid=7399128}}</ref> Motor connections from the brain to the spinal cord, and sensory connections from the spinal cord to the brain, both [[Biology:Decussation|cross sides]] in the brainstem. Visual input follows a more complex rule: the optic nerves from the two eyes come together at a point called the [[Biology:Optic chiasm|optic chiasm]], and half of the fibres from each nerve split off to join the other.<ref>{{cite book |author=Hellier, J. |title=The Brain, the Nervous System, and Their Diseases [3 volumes] |isbn=978-1-61069-338-7 |publisher=[[Company:ABC-CLIO|ABC-CLIO]] |year=2014 |page=1135 |url=https://books.google.com/books?id=SDi2BQAAQBAJ&pg=PA1135}}</ref> The result is that connections from the left half of the retina, in both eyes, go to the left side of the brain, whereas connections from the right half of the retina go to the right side of the brain.<ref name="Kolb 2">{{cite book |last1=Kolb |first1=B. |last2=Whishaw |first2=I.Q. |title=Introduction to Brain and Behavior |isbn=978-1-4641-3960-4 |publisher=Macmillan Higher Education |year=2013 |page=296 |url=https://books.google.com/books?id=teUkAAAAQBAJ}}</ref> Because each half of the retina receives light coming from the opposite half of the visual field, the functional consequence is that visual input from the left side of the world goes to the right side of the brain, and vice versa.<ref name="Berntson">{{cite book |last1=Berntson |first1=G. |last2=Cacioppo |first2=J. |title=Handbook of Neuroscience for the Behavioral Sciences, Volume 1 |publisher={{wipe|John Wiley & Sons}} |year=2009 |page=145 |isbn=978-0-470-08355-0 |url=https://books.google.com/books?id=LwdJhh8bOvwC&pg=PA145}}</ref> Thus, the right side of the brain receives somatosensory input from the left side of the body, and visual input from the left side of the visual field.<ref name="Sherwood">{{cite book |last1=Sherwood |first1=L. |title=Human Physiology: From Cells to Systems |isbn=978-1-133-70853-7 |publisher=Cengage Learning |year=2012 |page=181 |url=https://books.google.com/books?id=CZkJAAAAQBAJ&pg=PT181}}</ref><ref name="Kalat">{{cite book |author=Kalat, J |title=Biological Psychology |isbn=978-1-305-46529-9 |publisher=Cengage Learning |year=2015 |page=425 |url=https://books.google.com/books?id=EzZBBAAAQBAJ&pg=PA425}}</ref>

The left and right sides of the brain appear symmetrical, but they function asymmetrically.<ref name="Cowin">{{cite book |last1=Cowin |first1=S.C. |last2=Doty |first2=S.B. |title=Tissue Mechanics |isbn=978-0-387-49985-7 |publisher=Springer Science & Business Media |year=2007 |page=4 |url=https://books.google.com/books?id=8BJhRkat--YC&pg=PA4}}</ref> For example, the counterpart of the left-hemisphere motor area controlling the right hand is the right-hemisphere area controlling the left hand. There are, however, several important exceptions, involving language and spatial cognition. The left frontal lobe is dominant for language. If a key language area in the left hemisphere is damaged, it can leave the victim unable to speak or understand,<ref name="Cowin"/> whereas equivalent damage to the right hemisphere would cause only minor impairment to language skills.

A substantial part of current understanding of the interactions between the two hemispheres has come from the study of "[[Philosophy:Split-brain|split-brain]] patients"—people who underwent surgical transection of the corpus callosum in an attempt to reduce the severity of epileptic seizures.<ref name="Myers">{{cite book |last1=Morris |first1=C.G. |last2=Maisto |first2=A.A. |title=Understanding Psychology |isbn=978-0-205-76906-3 |publisher=Prentice Hall |year=2011 |page=56 |url=https://books.google.com/books?id=hoVWAAAAYAAJ}}</ref> These patients do not show unusual behaviour that is immediately obvious, but in some cases can behave almost like two different people in the same body, with the right hand taking an action and then the left hand undoing it.<ref name="Myers"/><ref name="Kolb 3">{{cite book |last1=Kolb |first1=B. |last2=Whishaw |first2=I.Q. |title=Introduction to Brain and Behavior (Loose-Leaf) |isbn=978-1-4641-3960-4 |publisher=Macmillan Higher Education |year=2013 |pages=524–549 |url=https://books.google.com/books?id=teUkAAAAQBAJ}}</ref> These patients, when briefly shown a picture on the right side of the point of visual fixation, are able to describe it verbally, but when the picture is shown on the left, are unable to describe it, but may be able to give an indication with the left hand of the nature of the object shown.<ref name="Kolb 3"/><ref name="Schacter">{{cite book |last1=Schacter |first1=D.L. |last2=Gilbert |first2=D.T. |last3=Wegner |first3=D.M. |title=Introducing Psychology |isbn=978-1-4292-1821-4 |publisher=Macmillan |year=2009 |page=80 |url=https://books.google.com/books?id=gt8lpZylVmkC&pg=PA80}}</ref>

===Emotion===
{{Main|Philosophy:Emotion}}
{{Further |Biology:Affective neuroscience}}
[[Philosophy:Emotion|Emotion]]s are generally defined as two-step multicomponent processes involving elicitation, followed by psychological feelings, appraisal, expression, autonomic responses, and action tendencies.<ref>{{cite book |last=Sander |first=David |editor1-last=Armony |editor1-first=J. |editor2-first=Patrik |editor2-last=Vuilleumier |title=The Cambridge handbook of human affective neuroscience |date=2013 |publisher=Cambridge Univ. Press |location=Cambridge |isbn=978-0-521-17155-7 |page=16 }}</ref> Attempts to localise basic emotions to certain brain regions have been controversial; some research found no evidence for specific locations corresponding to emotions, but instead found circuitry involved in general emotional processes. The [[Medicine:Amygdala|amygdala]], [[Biology:Orbitofrontal cortex|orbitofrontal cortex]], mid and anterior insula cortex and lateral [[Biology:Prefrontal cortex|prefrontal cortex]], appeared to be involved in generating the emotions, while weaker evidence was found for the [[Chemistry:Ventral tegmental area|ventral tegmental area]], [[Biology:Ventral pallidum|ventral pallidum]] and [[Biology:Nucleus accumbens|nucleus accumbens]] in incentive salience.<ref>{{cite journal |last1=Lindquist |first1=KA. |last2=Wager |first2=TD. |last3=Kober |first3=H |last4=Bliss-Moreau |first4=E |last5=Barrett |first5=LF |title=The brain basis of emotion: A meta-analytic review |journal=Behavioral and Brain Sciences |date=May 23, 2012 |volume=35 |issue=3 |pages=121–143 |doi=10.1017/S0140525X11000446|pmid=22617651 |pmc=4329228 }}</ref> Others, however, have found evidence of activation of specific regions, such as the [[Biology:Basal ganglia|basal ganglia]] in happiness, the [[Biology:Corpus callosum|subcallosal]] [[Biology:Cingulate cortex|cingulate cortex]] in sadness, and [[Medicine:Amygdala|amygdala]] in fear.<ref>{{cite journal |last1=Phan |first1=KL |last2=Wager |first2=Tor |last3=Taylor |first3=SF. |last4=Liberzon |first4=l |title=Functional Neuroanatomy of Emotion: A Meta-Analysis of Emotion Activation Studies in PET and fMRI |journal=NeuroImage |date=June 1, 2002 |volume=16 |issue=2 |pages=331–348 |doi=10.1006/nimg.2002.1087 |pmid=12030820|s2cid=7150871 }}</ref>

===Cognition===

The brain is responsible for [[Cognition|cognition]],<ref name="NHM preface - Cognition">{{cite book | last1=Malenka |first1=RC |last2=Nestler |first2=EJ |last3=Hyman |first3=SE | editor1-last=Sydor |editor1-first=A |editor2-last=Brown |editor2-first=RY | title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year=2009 | publisher=McGraw-Hill Medical | location=New York | isbn=978-0-07-148127-4 | page=xiii | edition=2nd | chapter=Preface }}</ref><ref name="NHMH_3e – Higher Cognitive Function and Behavioral Control" /> which functions through numerous processes and executive functions.<ref name="NHMH_3e – Higher Cognitive Function and Behavioral Control">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE, Holtzman DM | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-182770-6 | edition = 3rd | chapter = Chapter 14: Higher Cognitive Function and Behavioral Control}}</ref><ref name="NHMH_3e – pathways">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE, Holtzman DM | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-182770-6 | edition = 3rd | chapter=Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin}}</ref><ref name="Executive functions">{{cite journal | last1=Diamond |first1=A | title=Executive functions | journal=Annual Review of Psychology | volume=64 | pages=135–168 | year=2013 | pmid=23020641 | pmc=4084861 | doi=10.1146/annurev-psych-113011-143750 }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084861/figure/F4/ Figure 4: Executive functions and related terms] {{webarchive|url=https://web.archive.org/web/20180509181646/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084861/figure/F4/ |date=May 9, 2018 }}</ref> Executive functions include the ability to filter information and tune out irrelevant stimuli with [[Biology:Attentional control|attentional control]] and [[Cognitive inhibition|cognitive inhibition]], the ability to process and manipulate information held in [[Working memory|working memory]], the ability to think about multiple concepts simultaneously and switch tasks with [[Philosophy:Cognitive flexibility|cognitive flexibility]], the ability to inhibit [[Philosophy:Impulse (psychology)|impulses]] and prepotent responses with [[Philosophy:Inhibitory control|inhibitory control]], and the ability to determine the relevance of information or appropriateness of an action.<ref name="NHMH_3e – pathways" /><ref name="Executive functions" /> Higher order executive functions require the simultaneous use of multiple basic executive functions, and include [[Engineering:Planning|planning]], [[Prospection|prospection]] and fluid intelligence (i.e., reasoning and [[Problem solving|problem solving]]).<ref name="Executive functions" />

The [[Biology:Prefrontal cortex|prefrontal cortex]] plays a significant role in mediating executive functions.<ref name="NHMH_3e – Higher Cognitive Function and Behavioral Control" /><ref name="Executive functions" /><ref name="Goldstein">{{cite book | editor1-last=Goldstein |editor1-first=S. |editor2-last=Naglieri |editor2-first=J. | last1=Hyun |first1=J.C. |last2=Weyandt |first2=L.L. |last3=Swentosky |first3=A. | title=Handbook of Executive Functioning | date=2014 | publisher=Springer | location=New York | isbn=978-1-4614-8106-5 | pages=13–23 | chapter=Chapter 2: The Physiology of Executive Functioning | chapter-url=https://books.google.com/books?id=1e8VAgAAQBAJ&pg=PA13 }}</ref> Planning involves activation of the [[Biology:Dorsolateral prefrontal cortex|dorsolateral prefrontal cortex]] (DLPFC), [[Biology:Anterior cingulate cortex|anterior cingulate cortex]], angular prefrontal cortex, right prefrontal cortex, and [[Biology:Supramarginal gyrus|supramarginal gyrus]].<ref name="Goldstein"/> Working memory manipulation involves the DLPFC, [[Biology:Inferior frontal gyrus|inferior frontal gyrus]], and areas of the parietal cortex.<ref name="NHMH_3e – Higher Cognitive Function and Behavioral Control" /><!--The preceding ref supports this statement, but the corresponding statements from this textbook weren't included in the reference's quote parameter--><ref name="Goldstein" /> [[Philosophy:Inhibitory control|Inhibitory control]] involves multiple areas of the prefrontal cortex, as well as the [[Biology:Caudate nucleus|caudate nucleus]] and [[Biology:Subthalamic nucleus|subthalamic nucleus]].<ref name="Executive functions" /><ref name="Goldstein" /><ref name="NHMH_3e – Addiction and ADHD" />

==Physiology==

===Neurotransmission===
{{Main|Biology:Neurotransmission}}
{{Further | Biology:Summation (neurophysiology)}}
Brain activity is made possible by the interconnections of [[Biology:Neuron|neuron]]s that are linked together to reach their targets.{{sfn|Pocock|2006|p=68}} A neuron consists of a [[Biology:Soma|cell body]], [[Biology:Axon|axon]], and [[Biology:Dendrite|dendrite]]s. Dendrites are often extensive branches that receive information in the form of signals from the axon terminals of other neurons. The signals received may cause the neuron to initiate an [[Biology:Action potential|action potential]] (an electrochemical signal or nerve impulse) which is sent along its axon to the axon terminal, to connect with the dendrites or with the cell body of another neuron. An action potential is initiated at the [[Biology:Axon#Initial segment|initial segment]] of an axon, which contains a specialised complex of proteins.<ref>{{cite journal |last=Clark |first=B.D. |author2=Goldberg, E.M. |author3=Rudy, B. |title=Electrogenic tuning of the axon initial segment. |journal=The Neuroscientist |date=December 2009 |volume=15 |issue=6 |pages=651–68 |pmid=20007821 |doi=10.1177/1073858409341973 |pmc=2951114}}</ref> When an action potential reaches the axon terminal it triggers the release of a [[Biology:Neurotransmitter|neurotransmitter]] at a [[Biology:Synapse|synapse]] that propagates a signal that acts on the target cell.{{sfn|Pocock|2006|pp=70–74}} These chemical neurotransmitters include [[Biology:Dopamine|dopamine]], [[Chemistry:Serotonin|serotonin]], [[Chemistry:Gamma-Aminobutyric acid|GABA]], glutamate, and [[Chemistry:Acetylcholine|acetylcholine]].<ref name=NIMH2017 /> GABA is the major inhibitory neurotransmitter in the brain, and glutamate is the major excitatory neurotransmitter.<ref>{{cite book|last1=Purves|first1=Dale|title=Neuroscience|date=2011|publisher=Sinauer|location=Sunderland, Mass.|isbn=978-0-87893-695-3|page=139|edition=5.}}</ref> Neurons link at synapses to form [[Biology:Neural pathway|neural pathway]]s, [[Neural circuit|neural circuit]]s, and large elaborate [[Biology:Large-scale brain networks|network systems]] such as the [[Salience network|salience network]] and the [[Biology:Default mode network|default mode network]], and the activity between them is driven by the process of [[Biology:Neurotransmission|neurotransmission]].

===Metabolism===
[[File:PET-image.jpg|thumb|upright|alt=A flat oval object is surrounded by blue. The object is largely green-yellow, but contains a dark red patch at one end and a number of blue patches. |PET image of the human brain showing energy consumption]]

The brain consumes up to 20% of the energy used by the human body, more than any other organ.<ref name="power-sciam">{{cite web |last=Swaminathan |first=N |title=Why Does the Brain Need So Much Power? |url=http://www.scientificamerican.com/article/why-does-the-brain-need-s/ |work=Scientific American |access-date=November 19, 2010 |date=April 29, 2008 |url-status=live |archive-url=https://web.archive.org/web/20140127171142/http://www.scientificamerican.com/article/why-does-the-brain-need-s/ |archive-date=January 27, 2014  }}</ref> In humans, blood glucose is the primary source of energy for most cells and is critical for normal function in a number of tissues, including the brain.<ref name="Glucose-Glycogen storage review" /> The human brain consumes approximately 60% of blood glucose in fasted, sedentary individuals.<ref name="Glucose-Glycogen storage review">{{cite journal | vauthors = Wasserman DH | title = Four grams of glucose | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 296 | issue = 1 | pages = E11–21 | date = January 2009 | pmid = 18840763 | pmc = 2636990 | doi = 10.1152/ajpendo.90563.2008 | quote = Four grams of glucose circulates in the blood of a person weighing 70&nbsp;kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4&nbsp;g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated.&nbsp;... The brain consumes ~60% of the blood glucose used in the sedentary, fasted person.&nbsp;... The amount of glucose in the blood is preserved at the expense of glycogen reservoirs (Fig. 2). In postabsorptive humans, there are ~100&nbsp;g of glycogen in the liver and ~400&nbsp;g of glycogen in muscle. Carbohydrate oxidation by the working muscle can go up by ~10-fold with exercise, and yet after 1&nbsp;h, blood glucose is maintained at ~4&nbsp;g.&nbsp;... It is now well established that both insulin and exercise cause translocation of GLUT4 to the plasma membrane. Except for the fundamental process of GLUT4 translocation, [muscle glucose uptake (MGU)] is controlled differently with exercise and insulin. Contraction-stimulated intracellular signaling (52, 80) and MGU (34, 75, 77, 88, 91, 98) are insulin independent. Moreover, the fate of glucose extracted from the blood is different in response to exercise and insulin (91, 105). For these reasons, barriers to glucose flux from blood to muscle must be defined independently for these two controllers of MGU.}}</ref> Brain [[Biology:Metabolism|metabolism]] normally relies upon blood [[Chemistry:Glucose|glucose]] as an energy source, but during times of low glucose (such as [[Philosophy:Fasting|fasting]], endurance exercise, or limited [[Chemistry:Carbohydrate|carbohydrate]] intake), the brain uses [[Biology:Ketone bodies|ketone bodies]] for fuel with a smaller need for glucose. The brain can also utilize [[Chemistry:Lactic acid#Exercise and lactate|lactate during exercise]].<ref>{{cite journal |title=Lactate fuels the human brain during exercise |last1=Quistorff |first1=B |last2=Secher |first2=N |last3=Van Lieshout |first3=J |date=July 24, 2008 |journal=[[Biology:The FASEB Journal|The FASEB Journal]] |doi=10.1096/fj.08-106104 |pmid=18653766 |volume=22 |issue=10 |pages=3443–3449 |doi-access=free |s2cid=15394163 }}</ref> The brain stores glucose in the form of [[Biology:Glycogen|glycogen]], albeit in significantly smaller amounts than that found in the [[Biology:Liver|liver]] or [[Biology:Skeletal muscle|skeletal muscle]].<ref>{{cite journal |last=Obel |first=L.F. |author2=Müller, M.S. |author3=Walls, A.B. |author4=Sickmann, H.M. |author5=Bak, L.K. |author6=Waagepetersen, H.S. |author7= Schousboe, A. |title=Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. |journal=Frontiers in Neuroenergetics |date=2012 |volume=4 |page=3 |pmid=22403540 |doi=10.3389/fnene.2012.00003 |pmc=3291878|doi-access=free }}</ref> [[Chemistry:Fatty acid#Length of free fatty acid chains|Long-chain fatty acid]]s cannot cross the [[Biology:Blood–brain barrier|blood–brain barrier]], but the liver can break these down to produce ketone bodies. However, [[Chemistry:Short-chain fatty acid|short-chain fatty acid]]s (e.g., [[Chemistry:Butyric acid|butyric acid]], [[Chemistry:Propionic acid|propionic acid]], and [[Chemistry:Acetic acid|acetic acid]]) and the [[Chemistry:Fatty acid#Length of free fatty acid chains|medium-chain fatty acids]], octanoic acid and [[Chemistry:Heptanoic acid|heptanoic acid]], can cross the blood–brain barrier and be metabolised by [[Biology:Brain cell|brain cell]]s.<ref>{{cite journal |last1=Marin-Valencia |first1=I. |display-authors=0 |title=Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. |journal=Journal of Cerebral Blood Flow and Metabolism |date=February 2013 |volume=33 |issue=2 |pages=175–82 |pmid=23072752 |doi=10.1038/jcbfm.2012.151 |pmc=3564188}}</ref><ref name="SCFA MCT-mediated BBB passage - 2005 review">{{cite journal | author=Tsuji, A. | title=Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems | journal=NeuroRx | volume=2 | issue=1 | pages=54–62 | year=2005 | pmid=15717057 | pmc=539320 | doi=10.1602/neurorx.2.1.54 | quote=Uptake of valproic acid was reduced in the presence of medium-chain fatty acids such as hexanoate, octanoate, and decanoate, but not propionate or butyrate, indicating that valproic acid is taken up into the brain via a transport system for medium-chain fatty acids, not short-chain fatty acids.&nbsp;... Based on these reports, valproic acid is thought to be transported bidirectionally between blood and brain across the BBB via two distinct mechanisms, monocarboxylic acid-sensitive and medium-chain fatty acid-sensitive transporters, for efflux and uptake, respectively.}}</ref><ref name="SCFA MCT-mediated BBB passage - 2014 review">{{cite journal | last1=Vijay |first1=N. |last2=Morris |first2=M.E. | title=Role of monocarboxylate transporters in drug delivery to the brain | journal=Curr. Pharm. Des. | volume=20 | issue=10 | pages=1487–98 | year=2014 | pmid=23789956 | pmc=4084603 | doi=10.2174/13816128113199990462 | quote=Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate.&nbsp;... MCT1 and MCT4 have also been associated with the transport of short chain fatty acids such as acetate and formate which are then metabolized in the astrocytes [78].}}</ref>

Although the human brain represents only 2% of the body weight, it receives 15% of the cardiac output, 20% of total body oxygen consumption, and 25% of total body [[Chemistry:Glucose|glucose]] utilization.<ref>{{cite book |last=Clark |first=D.D. |author2=Sokoloff. L. |editor1=Siegel, G.J.|editor2=Agranoff, B.W.|editor3=Albers, R.W.|editor4=Fisher, S.K.|editor5=Uhler, M.D. |title=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |publisher=Lippincott |location=Philadelphia |year=1999 |pages=637–670 |isbn=978-0-397-51820-3}}</ref> The brain mostly uses glucose for energy, and deprivation of glucose, as can happen in [[Medicine:Hypoglycemia|hypoglycemia]], can result in loss of consciousness.<ref name="Mrsulja">{{cite book |author=Mrsulja, B.B. |title=Pathophysiology of Cerebral Energy Metabolism |isbn=978-1-4684-3348-7 |publisher=Springer Science & Business Media |year=2012 |pages=2–3 |url=https://books.google.com/books?id=8yzvBwAAQBAJ&pg=PA2}}</ref> The energy consumption of the brain does not vary greatly over time, but active regions of the cortex consume somewhat more energy than inactive regions, which forms the basis for the [[Biology:Functional neuroimaging|functional neuroimaging]] methods of [[Physics:Positron emission tomography|PET]] and fMRI.<ref>{{cite journal |last1=Raichle |first1=M. |year=2002 |title=Appraising the brain's energy budget |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |pages=10237–10239 |doi=10.1073/pnas.172399499 |pmid=12149485 |last2=Gusnard |first2=DA |pmc=124895 |issue=16|bibcode=2002PNAS...9910237R |doi-access=free }}</ref> These techniques provide a three-dimensional image of metabolic activity.<ref name="Steptoe">{{cite book |editor-last=Steptoe |editor-first=A. |last1=Gianaros |first1=Peter J. |last2=Gray |first2=Marcus A. |last3=Onyewuenyi |first3=Ikechukwu |last4=Critchley |first4=Hugo D.|title=Handbook of Behavioral Medicine |chapter=Neuroimaging Methods in Behavioral Medicine |isbn=978-0-387-09488-5 |publisher=Springer Science & Business Media |year=2010 |page=770 |chapter-url=https://books.google.com/books?id=Si9TtI5AGIEC&pg=PA770 |doi=10.1007/978-0-387-09488-5_50}}</ref> A preliminary study showed that brain metabolic requirements in humans peak at about five years old.<ref>{{Cite journal|last1=Kuzawa|first1=C. W.|last2=Chugani|first2=H. T.|last3=Grossman|first3=L. I.|last4=Lipovich|first4=L.|last5=Muzik|first5=O.|last6=Hof|first6=P. R.|last7=Wildman|first7=D. E.|last8=Sherwood|first8=C. C.|last9=Leonard|first9=W. R.|last10=Lange|first10=N.|date=2014-09-09|title=Metabolic costs and evolutionary implications of human brain development|journal=Proceedings of the National Academy of Sciences|volume=111|issue=36|pages=13010–13015|doi=10.1073/pnas.1323099111|issn=0027-8424|pmc=4246958|pmid=25157149|bibcode=2014PNAS..11113010K|doi-access=free}}</ref>

The function of [[Biology:Sleep|sleep]] is not fully understood; however, there is evidence that sleep enhances the clearance of metabolic waste products, some of which are potentially neurotoxic, from the brain and may also permit repair.<ref name="Glymphatic system and brain waste clearance 2017 review" /><ref>{{cite web |title=Brain may flush out toxins during sleep |url=http://www.ninds.nih.gov/news_and_events/news_articles/pressrelease_brain_sleep_10182013.htm |work=[[Organization:National Institutes of Health|National Institutes of Health]] |access-date=October 25, 2013 |url-status=live |archive-url=https://web.archive.org/web/20131020220815/http://www.ninds.nih.gov/news_and_events/news_articles/pressrelease_brain_sleep_10182013.htm |archive-date=October 20, 2013  }}</ref><ref name="Sleep – clearance of neurotoxic waste products">{{cite journal | vauthors = Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M | title = Sleep drives metabolite clearance from the adult brain | journal = Science | volume = 342 | issue = 6156 | pages = 373–377 | date = October 2013 | pmid = 24136970 | pmc = 3880190 | doi = 10.1126/science.1241224 | quote = Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.| bibcode = 2013Sci...342..373X }}</ref> Evidence suggests that the increased clearance of metabolic waste during sleep occurs via increased functioning of the [[Biology:Glymphatic system|glymphatic system]].<ref name="Glymphatic system and brain waste clearance 2017 review">{{cite journal | vauthors = Bacyinski A, Xu M, Wang W, Hu J | title = The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy | journal = Frontiers in Neuroanatomy | volume = 11 | page = 101 | date = November 2017 | pmid = 29163074 | pmc = 5681909 | doi = 10.3389/fnana.2017.00101 | quote = The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. &nbsp;... In addition to Aβ clearance, the glymphatic system may be involved in the removal of other interstitial solutes and metabolites. By measuring the lactate concentration in the brains and cervical lymph nodes of awake and sleeping mice, Lundgaard et al. (2017) demonstrated that lactate can exit the CNS via the paravascular pathway. Their analysis took advantage of the substantiated hypothesis that glymphatic function is promoted during sleep (Xie et al., 2013; Lee et al., 2015; Liu et al., 2017).| doi-access = free }}</ref> Sleep may also have an effect on cognitive function by weakening unnecessary connections.<ref>{{cite journal |url=https://pdfs.semanticscholar.org/6f9d/f7817534e55865bd1f6b7da6d2912bdbeaf3.pdf |archive-url=https://web.archive.org/web/20181226232857/https://pdfs.semanticscholar.org/6f9d/f7817534e55865bd1f6b7da6d2912bdbeaf3.pdf |url-status=dead |archive-date=2018-12-26 |last1=Tononi |first1=Guilio |last2=Cirelli |first2=Chiara |title=Perchance to Prune |journal=Scientific American |volume=309 |issue=2 |date=August 2013 |pages=34–39 |pmid=23923204|doi=10.1038/scientificamerican0813-34 |bibcode=2013SciAm.309b..34T |s2cid=54052089 }}</ref>

==Research==
The brain is not fully understood, and research is ongoing.<ref name=HCP2009 /> [[Neuroscientist]]s, along with researchers from allied disciplines, study how the human brain works. The boundaries between the specialties of [[Biology:Neuroscience|neuroscience]], [[Biology:Neurology|neurology]] and other disciplines such as [[Biology:Psychiatry|psychiatry]] have faded as they are all influenced by [[Basic research|basic research]] in neuroscience.

Neuroscience research has expanded considerably. The "Decade of the Brain", an initiative of the United States Government in the 1990s, is considered to have marked much of this increase in research,<ref>{{Cite journal |first1=E.G. |last1=Jones |first2=L.M. |last2=Mendell |title=Assessing the Decade of the Brain |journal=Science |doi=10.1126/science.284.5415.739 |date=April 30, 1999 |volume=284 |issue=5415 |page=739 |pmid=10336393 |bibcode = 1999Sci...284..739J|s2cid=13261978 }}</ref> and was followed in 2013 by the [[Biology:BRAIN Initiative|BRAIN Initiative]].<ref>{{cite web |title=A $4.5 Billion Price Tag for the BRAIN Initiative? |url=https://www.science.org/content/article/45-billion-price-tag-brain-initiative |website=Science {{!}} AAAS |date=June 5, 2014 |url-status=live |archive-url=https://web.archive.org/web/20170618154752/http://www.sciencemag.org/news/2014/06/45-billion-price-tag-brain-initiative |archive-date=June 18, 2017  }}</ref> The [[Human Connectome Project]] was a five-year study launched in 2009 to analyse the anatomical and functional connections of parts of the brain, and has provided much data.<ref name=HCP2009>{{cite journal |last1=Van Essen |first1=D.C. |display-authors=0 |title=The Human Connectome Project: A data acquisition perspective |journal=NeuroImage |date=October 2012 |volume=62 |issue=4 |pages=2222–2231 |doi=10.1016/j.neuroimage.2012.02.018|pmid=22366334 |pmc=3606888 }}</ref>
 
An emerging phase in research may be that of [[Simulation|simulating]] brain activity.<ref>{{Cite journal|last1=Fan|first1=Xue|last2=Markram|first2=Henry|date=2019-05-07|title=A Brief History of Simulation Neuroscience|journal=Frontiers in Neuroinformatics|volume=13|page=32|doi=10.3389/fninf.2019.00032|pmid=31133838|pmc=6513977|issn=1662-5196|doi-access=free}}</ref>

The chemistry of memory storage, logical thought processes, and conciousness are other areas of research. A hypothesis is that the brain stores memories through a construct of intermolecular and intramolecular network patterns of folded glycoproteins, and that memory may be encoded in hydrogen-bonding patterns.<ref name="Amtul">{{cite journal |last1=Amtul |first1=Z |last2=Rahman |first2=AU |title=Neural Plasticity and Memory: Is Memory Encoded in Hydrogen Bonding Patterns? |journal=The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry |date=February 2016 |volume=22 |issue=1 |pages=9-18 |doi=10.1177/1073858414547934 |pmid=25168338}}</ref><ref name="Chatterjee">{{cite journal |last1=Chatterjee |first1=S |last2=Bahl |first2=E |last3=Mukherjee |first3=U |last4=Walsh |first4=EN |last5=Shetty |first5=MS |last6=Yan |first6=AL |last7=Vanrobaeys |first7=Y |last8=Lederman |first8=JD |last9=Giese |first9=KP |last10=Michaelson |first10=J |last11=Abel |first11=T |title=Endoplasmic reticulum chaperone genes encode effectors of long-term memory. |journal=Science advances |date=25 March 2022 |volume=8 |issue=12 |pages=eabm6063 |doi=10.1126/sciadv.abm6063 |pmid=35319980}}</ref>

===Methods===
Information about the structure and function of the human brain comes from a variety of experimental methods, including animals and humans. Information about brain trauma and stroke has provided information about the function of parts of the brain and the effects of [[Medicine:Brain damage|brain damage]]. [[Biology:Neuroimaging|Neuroimaging]] is used to visualise the brain and record brain activity. [[Biology:Electrophysiology|Electrophysiology]] is used to measure, record and monitor the electrical activity of the cortex. Measurements may be of [[Biology:Local field potential|local field potential]]s of cortical areas, or of the activity of a single neuron. An [[Biology:Electroencephalography|electroencephalogram]] can record the electrical activity of the cortex using [[Physics:Electrode|electrode]]s placed non-invasively on the [[Medicine:Scalp|scalp]].<ref>{{cite journal | last1=Towle |first1=V.L. |display-authors=0 |title=The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy |journal=Electroencephalography and Clinical Neurophysiology |date=January 1993 |volume=86 |issue=1 |pages=1–6 |pmid=7678386 |doi=10.1016/0013-4694(93)90061-y}}</ref>{{sfn|Purves|2012|pp=632–633}}

Invasive measures include [[Biology:Electrocorticography|electrocorticography]], which uses electrodes placed directly on the exposed surface of the brain. This method is used in cortical stimulation mapping, used in the study of the relationship between cortical areas and their systemic function.<ref>{{cite journal |last1=Silverstein |first1=J. |title=Mapping the Motor and Sensory Cortices: A Historical Look and a Current Case Study in Sensorimotor Localization and Direct Cortical Motor Stimulation |journal=The Neurodiagnostic Journal |pmid=22558647 |url=http://www.readperiodicals.com/201203/2662763741.html |year=2012 |volume=52 |issue=1 |pages=54–68 |url-status=live |archive-url=https://web.archive.org/web/20121117021132/http://www.readperiodicals.com/201203/2662763741.html |archive-date=November 17, 2012  }}</ref> By using much smaller [[Biology:Microelectrode|microelectrode]]s, [[Biology:Single-unit recording|single-unit recording]]s can be made from a single neuron that give a high [[Angular resolution|spatial resolution]] and high [[Engineering:Temporal resolution|temporal resolution]]. This has enabled the linking of brain activity to behaviour, and the creation of neuronal maps.<ref>{{cite journal |last1=Boraud |first1=T. |last2=Bezard |first2=E. | year=2002 | title=From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control | journal=Progress in Neurobiology | volume=66 | issue=4 | pages=265–283 | doi=10.1016/s0301-0082(01)00033-8 |pmid=11960681 |s2cid=23389986 |display-authors=0}}</ref>

The development of [[Biology:Cerebral organoid|cerebral organoid]]s has opened ways for studying the growth of the brain, and of the cortex, and for understanding disease development, offering further implications for therapeutic applications.<ref name="Lancaster">{{cite journal |last1=Lancaster |first1=MA |last2=Renner |first2=M |last3=Martin |first3=CA |last4=Wenzel |first4=D |last5=Bicknell |first5=LS |last6=Hurles |first6=ME |last7=Homfray |first7=T |last8=Penninger |first8=JM |last9=Jackson |first9=AP |last10=Knoblich |first10=JA |title=Cerebral organoids model human brain development and microcephaly. |journal=Nature |date=September 19, 2013 |volume=501 |issue=7467 |pages=373–9 |doi=10.1038/nature12517 |pmid=23995685|pmc=3817409 |bibcode=2013Natur.501..373L }}</ref><ref name="Lee">{{cite journal |last1=Lee |first1=CT |last2=Bendriem |first2=RM |last3=Wu |first3=WW |last4=Shen |first4=RF |title=3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. |journal=Journal of Biomedical Science |date=August 20, 2017 |volume=24 |issue=1 |page=59 |doi=10.1186/s12929-017-0362-8 |pmid=28822354|pmc=5563385 |doi-access=free }}</ref>

===Imaging===
{{Further |Physics:Magnetic resonance imaging of the brain}}

[[Biology:Functional neuroimaging|Functional neuroimaging]] techniques show changes in brain activity that relate to the function of specific brain areas. One technique is [[Physics:Functional magnetic resonance imaging|functional magnetic resonance imaging]] (fMRI) which has the advantages over earlier methods of SPECT and [[Physics:Positron emission tomography|PET]] of not needing the use of [[Medicine:Nuclear medicine|radioactive materials]] and of offering a higher resolution.<ref>{{cite web |title=Magnetic Resonance, a critical peer-reviewed introduction; functional MRI |publisher=European Magnetic Resonance Forum |access-date=June 30, 2017 |url=http://www.magnetic-resonance.org/ch/11-03.html |url-status=live |archive-url=https://web.archive.org/web/20170602035337/http://www.magnetic-resonance.org/ch/11-03.html |archive-date=June 2, 2017  }}</ref> Another technique is [[Biology:Functional near-infrared spectroscopy|functional near-infrared spectroscopy]]. These methods rely on the [[Biology:Haemodynamic response|haemodynamic response]] that shows changes in brain activity in relation to changes in [[Biology:Cerebral circulation|blood flow]], useful in [[Biology:Brain mapping|mapping functions to brain areas]].<ref>{{cite journal |last1=Buxton |first1=R. |last2=Uludag |first2=K. |last3=Liu |first3=T. | year= 2004| title=Modeling the haemodynamic response to brain activation | journal=NeuroImage | volume= 23 | pages=S220–S233 | doi=10.1016/j.neuroimage.2004.07.013|pmid=15501093 |citeseerx=10.1.1.329.29 |s2cid=8736954 }}</ref> [[Physics:Resting state fMRI|Resting state fMRI]]
looks at the interaction of brain regions whilst the brain is not performing a specific task.<ref>{{cite journal |last1=Biswal |first1=B.B. |title=Resting state fMRI: a personal history |journal=NeuroImage|date=August 15, 2012|volume=62|issue=2|pages=938–44|pmid=22326802|doi=10.1016/j.neuroimage.2012.01.090|s2cid=93823 }}</ref> This is also used to show the [[Biology:Default mode network|default mode network]].

Any electrical current generates a magnetic field; [[Biology:Neural oscillation|neural oscillation]]s induce weak magnetic fields, and in functional [[Biology:Magnetoencephalography|magnetoencephalography]] the current produced can show localised brain function in high resolution.{{sfn|Purves|2012|p=20}} [[Physics:Tractography|Tractography]] uses MRI and [[Image analysis|image analysis]] to create [[3D modeling|3D images]] of the [[Biology:Nerve tract|nerve tract]]s of the brain. [[Biology:Connectogram|Connectogram]]s give a graphical representation of the [[Connectome|neural connections]] of the brain.<ref name="Kane">{{cite book |last1=Kane |first1=R.L. |last2=Parsons |first2=T.D. |title=The Role of Technology in Clinical Neuropsychology |isbn=978-0-19-023473-7 |publisher=[[Organization:Oxford University Press|Oxford University Press]] |year=2017 |page=399 |url=https://books.google.com/books?id=iuAwDgAAQBAJ |quote=Irimia, Chambers, Torgerson, and Van Horn (2012) provide a first-step graphic on how best to display connectivity findings, as is presented in Figure 13.15. This is referred to as a connectogram.}}</ref>

Differences in [[Biology:Brain morphometry|brain structure can be measured]] in some disorders, notably [[Medicine:Schizophrenia|schizophrenia]] and [[Medicine:Dementia|dementia]]. Different biological approaches using imaging have given more insight for example into the disorders of [[Biology:Biology of depression|depression]] and obsessive-compulsive disorder. A key source of information about the function of brain regions is the effects of damage to them.<ref>{{cite book | url=https://books.google.com/books?id=kiCtU8wBTfwC | title=Neuropsychology | last=Andrews | first=D.G. | publisher=Psychology Press | year=2001 | isbn=978-1-84169-103-9}}</ref>

Advances in [[Biology:Neuroimaging|neuroimaging]] have enabled objective insights into mental disorders, leading to faster diagnosis, more accurate prognosis, and better monitoring.<ref>{{cite web |author=Lepage, M. |date=2010 |title=Research at the Brain Imaging Centre |work=Douglas Mental Health University Institute |url=http://www.douglas.qc.ca/page/imagerie-cerebrale?locale=en |url-status=dead |archive-url=https://web.archive.org/web/20120305042011/http://www.douglas.qc.ca/page/imagerie-cerebrale?locale=en |archive-date=March 5, 2012 }}</ref>

===Gene and protein expression===
{{Main|Biology:Bioinformatics}}
[[Biology:Bioinformatics|Bioinformatics]] is a field of study that includes the creation and advancement of databases, and computational and statistical techniques, that can be used in studies of the human brain, particularly in the areas of [[Biology:Bioinformatics#Gene and protein expression|gene and protein expression]]. Bioinformatics and studies in [[Biology:Genomics|genomics]], and [[Biology:Functional genomics|functional genomics]], generated the need for [[Biology:DNA annotation|DNA annotation]], a [[Biology:Transcriptomics technologies|transcriptome technology]], identifying [[Biology:Gene|gene]]s, their locations and functions.<ref name="Steward">{{cite journal | title=Genome annotation for clinical genomic diagnostics: strengths and weaknesses | author=Steward, C.A. |display-authors=0 | pmid=28558813 | doi=10.1186/s13073-017-0441-1 | volume=9 | issue=1 | pmc=5448149 | year=2017 | journal=Genome Med | page=49 | doi-access=free }}</ref><ref>{{cite journal | title=GENCODE: the reference human genome annotation for The ENCODE Project. | author=Harrow, J. |display-authors=0 | pmid=22955987 | doi=10.1101/gr.135350.111 | pmc=3431492 | volume=22 | issue=9 | date=September 2012 | journal=Genome Res. | pages=1760–74}}</ref><ref name="Gibson and Muse">{{cite book|title=A primer of genome science|vauthors=Gibson G, Muse SV|date=April 20, 2009 |publisher=Sinauer Associates|isbn=9780878932368|edition=3rd|location=Sunderland, MA}}</ref> [[Biology:GeneCards|GeneCards]] is a major database.

{{as of|2017}}, just under 20,000 [[Biology:Human genome#Coding sequences (protein-coding genes)|protein-coding genes]] are seen to be expressed in the human,<ref name="Steward"/> and some 400 of these genes are brain-specific.<ref>{{Cite web|url=https://www.proteinatlas.org/humanproteome/brain|title=The human proteome in brain – The Human Protein Atlas|website=www.proteinatlas.org|access-date=September 29, 2017|url-status=live|archive-url=https://web.archive.org/web/20170929231550/https://www.proteinatlas.org/humanproteome/brain|archive-date=September 29, 2017}}</ref><ref>{{Cite journal|last1=Uhlén|first1=Mathias|last2=Fagerberg|first2=Linn|last3=Hallström|first3=Björn M.|last4=Lindskog|first4=Cecilia|last5=Oksvold|first5=Per|last6=Mardinoglu|first6=Adil|last7=Sivertsson|first7=Åsa|last8=Kampf|first8=Caroline|last9=Sjöstedt|first9=Evelina|date=January 23, 2015|title=Tissue-based map of the human proteome|journal=Science|volume=347|issue=6220|page=1260419|doi=10.1126/science.1260419|issn=0036-8075|pmid=25613900|s2cid=802377}}</ref> The data that has been provided on [[Biology:Gene expression|gene expression]] in the brain has fuelled further research into a number of disorders. The long term use of alcohol for example, has shown altered gene expression in the brain, and cell-type specific changes that may relate to [[Medicine:Alcoholism|alcohol use disorder]].<ref>{{cite journal|last=Warden|first=A|year=2017|title=Gene expression profiling in the human alcoholic brain.|journal=Neuropharmacology|volume=122|pages=161–174|pmid=28254370|doi=10.1016/j.neuropharm.2017.02.017|pmc=5479716}}</ref> These changes have been noted in the [[Biology:Synapse|synaptic]] [[Biology:Transcriptome|transcriptome]] in the prefrontal cortex, and are seen as a factor causing the drive to alcohol dependence, and also to other substance abuses.<ref>{{cite journal | title=Applying the new genomics to alcohol dependence. | author=Farris, S.P. |display-authors=0 | journal=Alcohol | year=2015 | pmid=25896098 | doi=10.1016/j.alcohol.2015.03.001 | volume=49 | issue=8 | pmc=4586299 | pages=825–36}}</ref>

Other related studies have also shown evidence of synaptic alterations and their loss, in the ageing brain. Changes in gene expression alter the levels of proteins in various neural pathways and this has been shown to be evident in synaptic contact dysfunction or loss. This dysfunction has been seen to affect many structures of the brain and has a marked effect on inhibitory neurons resulting in a decreased level of neurotransmission, and subsequent cognitive decline and disease.<ref name="Rozycka">{{cite journal|last1=Rozycka|first1=A|last2=Liguz-Lecznar|first2=M|title=The space where aging acts: focus on the GABAergic synapse.|journal=Aging Cell|date=August 2017|volume=16|issue=4|pages=634–643|doi=10.1111/acel.12605|pmid=28497576|pmc=5506442}}</ref><ref>{{cite journal|last1=Flores|first1=CE|last2=Méndez|first2=P|title=Shaping inhibition: activity dependent structural plasticity of GABAergic synapses.|journal=Frontiers in Cellular Neuroscience|date=2014|volume=8|page=327|doi=10.3389/fncel.2014.00327|pmid=25386117|pmc=4209871|doi-access=free}}</ref>

==Clinical significance==
===Injury===
[[Medicine:Brain damage|Injury to the brain]] can manifest in many ways. [[Medicine:Traumatic brain injury|Traumatic brain injury]], for example received in contact sport, after a [[Medicine:Falling (accident)|fall]], or a traffic or work accident, can be associated with both immediate and longer-term problems. Immediate problems may include bleeding within the brain, this may compress the brain tissue or damage its blood supply. [[Medicine:Cerebral contusion|Bruising]] to the brain may occur. Bruising may cause widespread damage to the nerve tracts that can lead to a condition of [[Medicine:Diffuse axonal injury|diffuse axonal injury]].<ref name="GE Health">{{cite web|url=http://www.medcyclopaedia.com/library/topics/volume_vi_1/b/BRAIN_INJURY_TRAUMATIC.aspx|archive-url=https://archive.today/20110526162429/http://www.medcyclopaedia.com/library/topics/volume_vi_1/b/BRAIN_INJURY_TRAUMATIC.aspx|url-status=dead|archive-date=May 26, 2011|title=Brain Injury, Traumatic|publisher=[[Company:General Electric|GE]]|work=Medcyclopaedia}}</ref> A [[Medicine:Skull fracture|fractured skull]], injury to a particular area, [[Medicine:Deafness|deafness]], and [[Medicine:Concussion|concussion]] are also possible immediate developments. In addition to the site of injury, the opposite side of the brain may be affected, termed a [[Medicine:Coup contrecoup injury|contrecoup]] injury. Longer-term issues that may develop include [[Medicine:Posttraumatic stress disorder|posttraumatic stress disorder]], and [[Medicine:Hydrocephalus|hydrocephalus]]. [[Medicine:Chronic traumatic encephalopathy|Chronic traumatic encephalopathy]] can develop following multiple [[Medicine:Head injury|head injuries]].<ref>{{Cite journal |last1=Dawodu |first1=S.T. |title=Traumatic Brain Injury (TBI) – Definition and Pathophysiology: Overview, Epidemiology, Primary Injury |url=http://emedicine.medscape.com/article/326510-overview#a3 |website=Medscape |date=March 9, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170409021001/http://emedicine.medscape.com/article/326510-overview#a3 |archive-date=April 9, 2017  }}</ref>

===Disease===
[[Medicine:Neurodegenerative disease|Neurodegenerative disease]]s result in progressive damage to different parts of the brain's function, and [[Biology:Aging brain|worsen with age]]. Common examples include [[Medicine:Dementia|dementia]] such as [[Medicine:Alzheimer's disease|Alzheimer's disease]], alcoholic dementia or [[Medicine:Vascular dementia|vascular dementia]]; [[Medicine:Parkinson's disease|Parkinson's disease]]; and other rarer infectious, genetic, or metabolic causes such as [[Medicine:Huntington's disease|Huntington's disease]], [[Medicine:Motor neuron disease|motor neuron disease]]s, HIV dementia, [[Medicine:Neurosyphilis|syphilis-related dementia]] and [[Medicine:Wilson's disease|Wilson's disease]]. Neurodegenerative diseases can affect different parts of the brain, and can affect movement, [[Memory|memory]], and cognition.{{sfn|Davidson's|2010|pp=1196-7}}

Cerebral atherosclerosis is [[Medicine:Atherosclerosis|atherosclerosis]] that affects the brain. It results from the build-up of [[Medicine:Atheroma|plaques]] formed of [[Chemistry:Cholesterol|cholesterol]], in the large arteries of the brain, and can be mild to significant. When significant, arteries can become narrowed enough to reduce blood flow. It contributes to the development of dementia, and has protein similarities to those found in Alzheimer’s disease.<ref name="NN2020">{{cite journal |vauthors=Wingo AP, Fan W, Duong DM, Gerasimov ES, Dammer EB, Liu Y, Harerimana NV, White B, Thambisetty M, Troncoso JC, Kim N, Schneider JA, Hajjar IM, Lah JJ, Bennett DA, Seyfried NT, Levey AI, Wingo TS |title=Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain |journal=Nat Neurosci |volume=23 |issue=6 |pages=696–700 |date=June 2020 |pmid=32424284 |pmc=7269838 |doi=10.1038/s41593-020-0635-5 |url=}}</ref>

The brain, although protected by the blood–brain barrier, can be affected by infections including [[Biology:Virus|virus]]es, [[Biology:Bacteria|bacteria]] and [[Biology:Fungi|fungi]]. Infection may be of the [[Medicine:Meninges|meninges]] ([[Medicine:Meningitis|meningitis]]), the brain matter ([[Medicine:Encephalitis|encephalitis]]), or within the brain matter (such as a cerebral abscess).{{sfn|Davidson's|2010|pp=1205-15}} Rare prion diseases including [[Medicine:Creutzfeldt–Jakob disease|Creutzfeldt–Jakob disease]] and its [[Medicine:Variant Creutzfeldt–Jakob disease|variant]], and [[Medicine:Kuru (disease)|kuru]] may also affect the brain.{{sfn|Davidson's|2010|pp=1205-15}}

===Tumours===
[[Medicine:Brain tumor|Brain tumours]] can be either benign or cancerous. Most malignant tumours [[Medicine:Metastasis|arise from another part of the body]], most commonly from the lung, [[Medicine:Breast cancer|breast]] and [[Medicine:Melanoma|skin]].{{sfn|Davidson's|2010|pp=1216-7}} Cancers of brain tissue can also occur, and originate from any tissue in and around the brain. [[Medicine:Meningioma|Meningioma]], cancer of the meninges around the brain, is more common than cancers of brain tissue.{{sfn|Davidson's|2010|pp=1216-7}} Cancers within the brain may cause symptoms related to their size or position, with symptoms including headache and nausea, or the gradual development of focal symptoms such as gradual difficulty seeing, swallowing, talking, or as a change of mood.{{sfn|Davidson's|2010|pp=1216-7}} Cancers are in general investigated through the use of CT scans and MRI scans. A variety of other tests including blood tests and lumbar puncture may be used to investigate for the cause of the cancer and evaluate the type and [[Medicine:Cancer staging|stage]] of the cancer.{{sfn|Davidson's|2010|pp=1216-7}} The [[Biology:Corticosteroid|corticosteroid]] [[Biology:Dexamethasone|dexamethasone]] is often given to decrease the swelling of brain tissue around a tumour. Surgery may be considered, however given the complex nature of many tumours or based on tumour stage or type, radiotherapy or [[Medicine:Chemotherapy|chemotherapy]] may be considered more suitable.{{sfn|Davidson's|2010|pp=1216-7}}

===Mental disorders===
[[Medicine:Mental disorder|Mental disorder]]s, such as depression, [[Medicine:Schizophrenia|schizophrenia]], [[Medicine:Bipolar disorder|bipolar disorder]], [[Medicine:Posttraumatic stress disorder|posttraumatic stress disorder]], [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]], obsessive-compulsive disorder, [[Medicine:Tourette syndrome|Tourette syndrome]], and [[Medicine:Addiction|addiction]], are known to relate to the functioning of the brain.<ref name="NHMH_3e – Addiction and ADHD">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE, Holtzman DM | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-182770-6 | edition = 3rd | chapter = Chapter 14: Higher Cognitive Function and Behavioral Control | quote =In conditions in which prepotent responses tend to dominate behavior, such as in drug addiction, where drug cues can elicit drug seeking (Chapter 16), or in attention deficit hyperactivity disorder (ADHD; described below), significant negative consequences can result.&nbsp;... ADHD can be conceptualized as a disorder of executive function; specifically, ADHD is characterized by reduced ability to exert and maintain cognitive control of behavior. Compared with healthy individuals, those with ADHD have diminished ability to suppress inappropriate prepotent responses to stimuli (impaired response inhibition) and diminished ability to inhibit responses to irrelevant stimuli (impaired interference suppression).&nbsp;... Functional neuroimaging in humans demonstrates activation of the prefrontal cortex and caudate nucleus (part of the dorsal striatum) in tasks that demand inhibitory control of behavior.&nbsp;... Early results with structural MRI show a thinner cerebral cortex, across much of the cerebrum, in ADHD subjects compared with age-matched controls, including areas of [the] prefrontal cortex involved in working memory and attention.}}</ref><ref name=NIMH2017>{{cite web |title=NIMH » Brain Basics |url=https://www.nimh.nih.gov/health/educational-resources/brain-basics/brain-basics.shtml |website=www.nimh.nih.gov |access-date=March 26, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170326230311/https://www.nimh.nih.gov/health/educational-resources/brain-basics/brain-basics.shtml |archive-date=March 26, 2017  }}</ref><ref name="Addiction - brain disease review">{{cite journal | last1=Volkow |first1=N.D. |last2=Koob |first2=G.F. |last3=McLellan |first3=A.T. | title=Neurobiologic advances from the brain disease model of addiction | journal=The New England Journal of Medicine | volume=374 | issue=4 | pages=363–371 | date=January 2016 | pmid=26816013 | pmc=6135257 | doi=10.1056/NEJMra1511480}}</ref> Treatment for mental disorders may include [[Medicine:Psychotherapy|psychotherapy]], [[Biology:Psychiatry|psychiatry]], [[Philosophy:Social interventionism|social intervention]] and personal [[Medicine:Recovery model|recovery]] work or cognitive behavioural therapy; the underlying issues and associated prognoses vary significantly between individuals.<ref name="Simpson">{{cite book |last1=Simpson |first1=J.M. |last2=Moriarty |first2=G.L. |title=Multimodal Treatment of Acute Psychiatric Illness: A Guide for Hospital Diversion |publisher=Columbia University Press |year=2013 |pages=22–24 |isbn=978-0-231-53609-7 |url=https://books.google.com/books?id=MbtkAgAAQBAJ&pg=PA22}}</ref>

===Epilepsy===
Epileptic seizures are thought to relate to abnormal electrical activity.{{sfn|Davidson's|2010|pp=1172-9}} Seizure activity can manifest as absence of consciousness, focal effects such as limb movement or impediments of speech, or be generalized in nature.{{sfn|Davidson's|2010|pp=1172-9}} [[Medicine:Status epilepticus|Status epilepticus]] refers to a seizure or series of seizures that have not terminated within 5 minutes.<ref name="foundation">{{cite web |title=Status Epilepticus |url=https://www.epilepsy.com/learn/challenges-epilepsy/seizure-emergencies/status-epilepticus |website=Epilepsy Foundation}}</ref> Seizures have a large number of causes, however many seizures occur without a definitive cause being found. In a person with [[Medicine:Epilepsy|epilepsy]], risk factors for further seizures may include sleeplessness, drug and alcohol intake, and stress. Seizures may be assessed using [[Medicine:Blood test|blood test]]s, EEG and various [[Medicine:Medical imaging|medical imaging]] techniques based on the [[Medicine:Medical history|medical history]] and medical examination findings.{{sfn|Davidson's|2010|pp=1172-9}} In addition to treating an underlying cause and reducing exposure to risk factors, [[Chemistry:Anticonvulsant|anticonvulsant]] medications can play a role in preventing further seizures.{{sfn|Davidson's|2010|pp=1172-9}}

===Congenital===
Some brain disorders, such as [[Medicine:Tay–Sachs disease|Tay–Sachs disease]],<ref name="Moore">{{cite book |last=Moore |first=S.P. |title=The Definitive Neurological Surgery Board Review |publisher=Lippincott Williams & Wilkins |isbn=978-1-4051-0459-3 |page=112 |year=2005 |url=https://books.google.com/books?id=mkK1a4mEx3IC&pg=PA112}}</ref> are congenital and linked to [[Biology:Mutation|genetic]] and [[Biology:Chromosome abnormality|chromosomal]] mutations.<ref name="Pennington">{{cite book |last=Pennington |first=B.F. |title=Diagnosing Learning Disorders, Second Edition: A Neuropsychological Framework |publisher=Guilford Press |isbn=978-1-60623-786-1 |pages=3–10 |year=2008 |url=https://books.google.com/books?id=LVV10L62z6kC&pg=PA3}}</ref> A rare group of congenital cephalic disorders known as [[Medicine:Lissencephaly|lissencephaly]] is characterised by the lack of, or inadequacy of, cortical folding.<ref name="Govaert">{{cite book |last1=Govaert |first1=P. |last2=de Vries |first2=L.S. |title=An Atlas of Neonatal Brain Sonography: (CDM 182–183) |publisher={{wipe|John Wiley & Sons}} |isbn=978-1-898683-56-8 |pages=89–92 |year=2010 |url=https://books.google.com/books?id=FzcaxpvV1JUC&pg=PA89}}</ref> Normal [[Biology:Prenatal development|development]] of the brain can be affected during [[Medicine:Pregnancy|pregnancy]] by nutritional deficiencies,<ref name="Perese">{{cite book |last=Perese |first=E.F. |title=Psychiatric Advanced Practice Nursing: A Biopsychsocial Foundation for Practice |publisher=F.A. Davis |isbn=978-0-8036-2999-8 |pages=82–88 |year=2012 |url=https://books.google.com/books?id=6X_2AAAAQBAJ&pg=PA82}}</ref> [[Biology:Teratology|teratogen]]s,<ref name="Kearney">{{cite book |last1=Kearney |first1=C. |last2=Trull |first2=T.J. |title=Abnormal Psychology and Life: A Dimensional Approach |publisher=Cengage Learning |isbn=978-1-337-09810-6 |page=395 |year=2016  |url=https://books.google.com/books?id=B9q5DQAAQBAJ&pg=PA395}}</ref> infectious diseases,<ref name="Stevenson">{{cite book |last1=Stevenson |first1=D.K. |last2=Sunshine |first2=P. |last3=Benitz |first3=W.E. |title=Fetal and Neonatal Brain Injury: Mechanisms, Management and the Risks of Practice |publisher={{wipe|Cambridge University Press}} |isbn=978-0-521-80691-6 |page=191 |year=2003 |url=https://books.google.com/books?id=RuekFAj_tIAC&pg=PA191}}</ref> and by the use of recreational drugs, including alcohol (which may result in fetal alcohol spectrum disorders).<ref name="Perese"/><ref name="Dewhurst">{{cite book |last=Dewhurst |first=John |title=Dewhurst's Textbook of Obstetrics and Gynaecology |publisher={{wipe|John Wiley & Sons}} |isbn=978-0-470-65457-6 |page=43 |year=2012 |url=https://books.google.com/books?id=HfakBRceodcC&pg=PA43}}</ref>
Most [[Medicine:Cerebral arteriovenous malformation|cerebral arteriovenous malformation]]s are congenital, these tangled networks of blood vessels may remain without symptoms but at their worst may rupture and cause [[Medicine:Intracranial hemorrhage|intracranial hemorrhaging]].<ref name="NINDS">{{cite web |title=Arteriovenous Malformations (AVMs) {{!}} National Institute of Neurological Disorders and Stroke |url=https://www.ninds.nih.gov/health-information/disorders/arteriovenous-malformations-avms?search-term=arteriovenous%20mal |website=www.ninds.nih.gov |access-date=8 February 2023}}</ref>

===Stroke===
{{Main|Medicine:Stroke}}
[[File:Parachemableedwithedema.png|thumb|upright|[[CT scan|CT scan]] of a cerebral hemorrhage, showing an intraparenchymal bleed (bottom arrow) with surrounding edema (top arrow)]]

<!--Definitions and symptoms-->A [[Medicine:Stroke|stroke]] is a [[Medicine:Ischemia|decrease in blood supply]] to an area of the brain causing [[Biology:Cell death|cell death]] and [[Medicine:Brain damage#Causes|brain injury]]. This can lead to a wide range of [[Medicine:Stroke#Signs and symptoms|symptoms]], including the "[[Medicine:FAST (stroke)|FAST]]" symptoms of facial droop, arm weakness, and speech difficulties (including [[Medicine:Dysarthria|with speaking]] and finding words or forming sentences).<ref>{{cite journal |last1=Harbison |first1=J. |last2=Massey |first2=A. |last3=Barnett |first3=L. |last4=Hodge |first4=D. |last5=Ford |first5=G.A. | title=Rapid ambulance protocol for acute stroke | journal=Lancet | volume=353 | issue=9168 | page=1935 | date=June 1999 | pmid=10371574 | doi=10.1016/S0140-6736(99)00966-6 |s2cid=36692451 }}</ref> Symptoms relate to the function of the affected area of the brain and can point to the likely site and cause of the stroke. Difficulties with movement, speech, or sight usually relate to the cerebrum, whereas [[Medicine:Ataxia|imbalance]], [[Medicine:Diplopia|double vision]], [[Medicine:Vertigo|vertigo]] and symptoms affecting more than one side of the body usually relate to the brainstem or cerebellum.{{sfn|Davidson's|2010|p=1183}}

Most strokes result from loss of blood supply, typically because of an [[Medicine:Embolus|embolus]], rupture of a [[Medicine:Atheroma|fatty plaque]] causing [[Medicine:Thrombus|thrombus]], or narrowing of small arteries. Strokes can also result from [[Medicine:Stroke#Hemorrhagic|bleeding within the brain]].{{sfn|Davidson's|2010|pp=1180-1}} [[Medicine:Transient ischemic attack|Transient ischaemic attack]]s (TIAs) are strokes in which symptoms resolve within 24 hours.{{sfn|Davidson's|2010|pp=1180-1}} Investigation into the stroke will involve a medical examination (including a neurological examination) and the taking of a [[Medicine:Medical history|medical history]], focusing on the duration of the symptoms and risk factors (including [[Medicine:Hypertension|high blood pressure]], [[Medicine:Atrial fibrillation|atrial fibrillation]], and [[Chemistry:Tobacco smoking|smoking]]).{{sfn|Davidson's|2010|pp=1181, 1183-1185}} Further investigation is needed in younger patients.{{sfn|Davidson's|2010|pp=1183-1185}} An ECG and [[Engineering:Biotelemetry|biotelemetry]] may be conducted to identify [[Medicine:Atrial fibrillation|atrial fibrillation]]; an [[Physics:Ultrasound|ultrasound]] can investigate narrowing of the carotid arteries; an echocardiogram can be used to look for clots within the heart, [[Medicine:Valvular heart disease|diseases of the heart valves]] or the presence of a patent foramen ovale.{{sfn|Davidson's|2010|pp=1183-1185}} [[Medicine:Blood test|Blood test]]s are routinely done as part of the [[Medicine:Medical diagnosis#Other diagnostic procedure methods|workup]] including [[Medicine:Diabetes mellitus#Diagnosis|diabetes tests]] and a [[Chemistry:Lipid profile|lipid profile]].{{sfn|Davidson's|2010|pp=1183-1185}}

Some treatments for stroke are time-critical. These include clot dissolution or [[Medicine:Embolectomy|surgical removal of a clot]] for [[Medicine:Brain ischemia|ischaemic strokes]], and [[Medicine:Decompression (surgery)|decompression]] for [[Medicine:Intracranial hemorrhage|haemorrhagic strokes]].{{sfn|Davidson's|2010|pp=1185-1189}}<ref>{{cite journal |last1=Goyal |first1=M. |display-authors=0 |title=Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials |journal=The Lancet |date=April 2016 |volume=387 |issue=10029 |pages=1723–1731 |doi=10.1016/S0140-6736(16)00163-X |pmid=26898852 |s2cid=34799180 }}</ref> As stroke is time critical,<ref>{{cite journal |last1=Saver |first1=J. L. |title=Time is brain—quantified |journal=Stroke |date=December 8, 2005 |volume=37 |issue=1 |pages=263–266 |doi=10.1161/01.STR.0000196957.55928.ab|pmid=16339467 |doi-access=free }}</ref> hospitals and even pre-hospital care of stroke involves expedited investigations – usually a [[CT scan]] to investigate for a haemorrhagic stroke and a CT or MR angiogram to evaluate arteries that supply the brain.{{sfn|Davidson's|2010|pp=1183-1185}} MRI scans, not as widely available, may be able to demonstrate the affected area of the brain more accurately, particularly with ischaemic stroke.{{sfn|Davidson's|2010|pp=1183-1185}}

Having experienced a stroke, a person may be admitted to a stroke unit, and treatments may be directed as preventing future strokes, including ongoing anticoagulation (such as [[Chemistry:Aspirin|aspirin]] or [[Chemistry:Clopidogrel|clopidogrel]]), [[Chemistry:Antihypertensive drug|antihypertensives]], and [[Chemistry:Lipid-lowering agent|lipid-lowering drugs]].{{sfn|Davidson's|2010|pp=1185-1189}} A multidisciplinary team including speech pathologists, physiotherapists, [[Medicine:Occupational therapist|occupational therapist]]s, and [[Social:Psychologist|psychologist]]s plays a large role in supporting a person affected by a stroke and their [[Medicine:Physical medicine and rehabilitation|rehabilitation]].<ref>{{cite journal |last1=Winstein |first1=C.J. |display-authors=0 |title=Guidelines for adult stroke rehabilitation and recovery |journal=Stroke |date=June 2016 |volume=47 |issue=6 |pages=e98–e169 |doi=10.1161/STR.0000000000000098|pmid=27145936 |s2cid=4967333 |doi-access=free }}</ref>{{sfn|Davidson's|2010|pp=1183-1185}} A history of stroke increases the risk of developing dementia by around 70%, and recent stroke increases the risk by around 120%.<ref>{{Cite journal|last1=Kuźma|first1=Elżbieta|last2=Lourida|first2=Ilianna|last3=Moore|first3=Sarah F.|last4=Levine|first4=Deborah A.|last5=Ukoumunne|first5=Obioha C.|last6=Llewellyn|first6=David J.|date=November 2018 |title=Stroke and dementia risk: A systematic review and meta-analysis|journal=Alzheimer's & Dementia |volume=14 |issue=11 |pages=1416–1426 |doi=10.1016/j.jalz.2018.06.3061 |pmid=30177276|pmc=6231970|issn=1552-5260}}</ref>

===Brain death===
{{Main|Medicine:Brain death}}
Brain death refers to an irreversible total loss of brain function.<ref name="GOILA2009">{{cite journal |last1=Goila |first1=AK |last2=Pawar |first2=M |title=The diagnosis of brain death |journal=Indian Journal of Critical Care Medicine |date=2009 |volume=13 |issue=1 |pages=7–11 |doi=10.4103/0972-5229.53108|pmid=19881172 |pmc=2772257 |doi-access=free }}</ref><ref name=":0">{{Cite journal |last=Wijdicks |first=EFM |date=January 8, 2002 |title=Brain death worldwide: accepted fact but no global consensus in diagnostic criteria |journal=Neurology |volume=58 |issue=1 |pages=20–25 |pmid=11781400 |doi=10.1212/wnl.58.1.20|s2cid=219203458 }}</ref> This is characterised by [[Medicine:Coma|coma]], loss of [[Biology:Reflex|reflex]]es, and apnoea,<ref name=GOILA2009/> however, the declaration of brain death varies geographically and is not always accepted.<ref name=":0" /> In some countries there is also a defined syndrome of [[Medicine:Brainstem death|brainstem death]].<ref>{{cite journal |last1=Dhanwate |first1=AD |title=Brainstem death: A comprehensive review in Indian perspective. |journal=Indian Journal of Critical Care Medicine |date=September 2014 |volume=18 |issue=9 |pages=596–605 |pmid=25249744 |doi=10.4103/0972-5229.140151 |pmc=4166875 |doi-access=free }}</ref> Declaration of brain death can have profound implications as the declaration, under the principle of [[Medicine:Futile medical care|medical futility]], will be associated with the withdrawal of life support,{{sfn|Davidson's|2010|p=1158}} and as those with brain death often have organs suitable for [[Medicine:Organ donation|organ donation]].<ref name=":0" />{{sfn|Davidson's|2010|p=200}} The process is often made more difficult by poor communication with patients' families.<ref name="Urden">{{cite book |last1=Urden |first1=L.D. |last2=Stacy |first2=K.M. |last3=Lough |first3=M.E. |title=Priorities in Critical Care Nursing – E-Book |publisher=Elsevier Health Sciences |isbn=978-0-323-29414-0 |pages=112–113 |year=2013 |url=https://books.google.com/books?id=lLvwAwAAQBAJ&pg=PA112}}</ref>

When brain death is suspected, reversible [[Medicine:Differential diagnosis|differential diagnoses]] such as, electrolyte, neurological and drug-related cognitive suppression need to be excluded.<ref name="GOILA2009" />{{sfn|Davidson's|2010|p=1158}} Testing for reflexes{{efn|Including the vestibulo-ocular reflex, [[Biology:Corneal reflex|corneal reflex]], gag reflex and dilation of the pupils in response to light,{{sfn|Davidson's|2010|p=1158}}}} can be of help in the decision, as can the absence of response and breathing.{{sfn|Davidson's|2010|p=1158}} Clinical observations, including a total lack of responsiveness, a known diagnosis, and neural imaging evidence, may all play a role in the decision to pronounce brain death.<ref name="GOILA2009" />

==Society and culture==
[[Biology:Neuroanthropology|Neuroanthropology]] is the study of the relationship between culture and the brain. It explores how the brain gives rise to culture, and how culture influences brain development.<ref>{{Cite journal |last1=Domínguez |first1=J.F. |last2=Lewis |first2=E.D. |last3=Turner |first3=R. |last4=Egan |first4=G.F. |editor1-last=Chiao |editor1-first=J.Y. |title=The Brain in Culture and Culture in the Brain: A Review of Core Issues in Neuroanthropology |journal=Progress in Brain Research |date=2009 |volume=178 |pages=43–6 |doi=10.1016/S0079-6123(09)17804-4 |pmid=19874961 |series=Special issue: Cultural Neuroscience: Cultural Influences on Brain Function |isbn=978-0-444-53361-6 }}</ref> Cultural differences and their relation to brain development and structure are researched in different fields.<ref name="Cultural">{{cite web |title=Cultural Environment Influences Brain Function {{!}} Psych Central News |url=https://psychcentral.com/news/2010/08/04/cultural-environment-influences-brain-function/16380.html |website=Psych Central News |date=August 4, 2010 |url-status=live |archive-url=https://web.archive.org/web/20170117094114/http://psychcentral.com/news/2010/08/04/cultural-environment-influences-brain-function/16380.html |archive-date=January 17, 2017  }}</ref>

===The mind===
{{Main |Cognition |Philosophy:Mind}}
[[File:Phineas gage - 1868 skull diagram.jpg|thumb|upright|The skull of Phineas Gage, with the path of the iron rod that passed through it without killing him, but altering his cognition. The case helped to convince people that mental functions were localised in the brain.<ref name=Macmillan/>]]

The [[Philosophy:Philosophy of mind|philosophy of the mind]] studies such issues as the problem of understanding [[Philosophy:Consciousness|consciousness]] and the [[Philosophy:Mind–body problem|mind–body problem]]. The relationship between the brain and the [[Philosophy:Mind|mind]] is a significant challenge both philosophically and scientifically. This is because of the difficulty in explaining how mental activities, such as thoughts and emotions, can be implemented by physical structures such as neurons and [[Biology:Synapse|synapse]]s, or by any other type of physical mechanism. This difficulty was expressed by Gottfried Leibniz in the analogy known as ''Leibniz's Mill'':

{{Blockquote |One is obliged to admit that perception and what depends upon it is inexplicable on mechanical principles, that is, by figures and motions. In imagining that there is a machine whose construction would enable it to think, to sense, and to have perception, one could conceive it enlarged while retaining the same proportions, so that one could enter into it, just like into a windmill. Supposing this, one should, when visiting within it, find only parts pushing one another, and never anything by which to explain a perception.

::— Leibniz, [[Philosophy:Monadology|Monadology]]<ref>{{cite book |author=Rescher, N. |title=G. W. Leibniz's Monadology |year=1992 |publisher=Psychology Press |isbn=978-0-415-07284-7 |page=83}}</ref>}}

Doubt about the possibility of a mechanistic explanation of thought drove [[Biography:René Descartes|René Descartes]], and most other philosophers along with him, to dualism: the belief that the mind is to some degree independent of the brain.<ref>{{cite book |last=Hart |first=WD |year=1996 |editor=Guttenplan S |title=A Companion to the Philosophy of Mind |publisher=Blackwell |pages=265–267}}</ref> There has always, however, been a strong argument in the opposite direction. There is clear empirical evidence that physical manipulations of, or injuries to, the brain (for example by drugs or by lesions, respectively) can affect the mind in potent and intimate ways.<ref name=Churchland>{{cite book |last=Churchland |first=P.S. |title=Neurophilosophy |publisher=MIT Press |year=1989 |isbn=978-0-262-53085-9 |chapter-url=https://books.google.com/books?id=hAeFMFW3rDUC |chapter=Ch. 8}}</ref><ref>{{cite journal |last1=Selimbeyoglu |first1=Aslihan |last2=Parvizi |first2=J |title=Electrical stimulation of the human brain: perceptual and behavioral phenomena reported in the old and new literature |journal=Frontiers in Human Neuroscience |date=2010 |volume=4 |page=46 |doi=10.3389/fnhum.2010.00046 |pmid=20577584 |pmc=2889679|doi-access=free }}</ref> In the 19th century, the case of [[Biography:Phineas Gage|Phineas Gage]], a railway worker who was injured by a stout iron rod passing through his brain, convinced both researchers and the public that cognitive functions were localised in the brain.<ref name=Macmillan>{{cite book |last=Macmillan |first=Malcolm B. |year=2000 |title=An Odd Kind of Fame: Stories of Phineas Gage |publisher=MIT Press |url=https://books.google.com/books?id=Qx4fMsTqGFYC |isbn=978-0-262-13363-0}}</ref> Following this line of thinking, a large body of empirical evidence for a close relationship between brain activity and mental activity has led most neuroscientists and contemporary philosophers to be [[Philosophy:Materialism|materialists]], believing that mental phenomena are ultimately the result of, or reducible to, physical phenomena.<ref>Schwartz, J.H. '' Appendix D: Consciousness and the Neurobiology of the Twenty-First Century''. In Kandel, E.R.; Schwartz, J.H.; Jessell, T.M. (2000). ''Principles of Neural Science, 4th Edition''.</ref>

===Brain size===
{{Main|Biology:Brain size}}
The size of the brain and a person's [[Philosophy:Intelligence|intelligence]] are not strongly related.<ref>{{Cite book |url=https://books.google.com/books?id=8DlS0gfO_QUC&pg=PT89 |title=50 Great Myths of Popular Psychology: Shattering Widespread Misconceptions about Human Behavior |last1=Lilienfeld |first1=S.O. |last2=Lynn |first2=S.J. |last3=Ruscio |first3=J. |last4=Beyerstein |first4=B.L. |date=2011 |publisher=John Wiley & Sons |isbn=978-1-4443-6074-5 |page=89}}</ref> Studies tend to indicate small to moderate [[Correlation|correlation]]s (averaging around 0.3 to 0.4) between brain volume and [[Philosophy:Intelligence quotient|IQ]].<ref>{{cite journal |last=McDaniel |first=M. |journal=Intelligence |volume=33 |issue=4 |pages=337–346 |year=2005 |url=http://www.people.vcu.edu/~mamcdani/Big-Brained%20article.pdf |title=Big-brained people are smarter |doi=10.1016/j.intell.2004.11.005 |url-status=live |archive-url=https://web.archive.org/web/20140906221726/http://www.people.vcu.edu/~mamcdani/Big-Brained%20article.pdf |archive-date=September 6, 2014  }}</ref> The most consistent associations are observed within the frontal, temporal, and parietal lobes, the hippocampi, and the cerebellum, but these only account for a relatively small amount of variance in IQ, which itself has only a partial relationship to general intelligence and real-world performance.<ref>{{cite journal |last1=Luders |first1=E. |display-authors=0 |title=Mapping the relationship between cortical convolution and intelligence: effects of gender |journal=Cerebral Cortex |date=September 2008 |volume=18 |issue=9 |pages=2019–26 |pmid=18089578 |doi=10.1093/cercor/bhm227 |pmc=2517107}}</ref><ref>{{Cite journal |last1=Hoppe |first1=C |last2=Stojanovic |first2=J |year=2008 |title=High-Aptitude Minds |journal=Scientific American Mind |volume=19 |issue=4 |pages=60–67 |doi=10.1038/scientificamericanmind0808-60}}</ref>

Other animals, including whales and elephants have larger brains than humans. However, when the [[Physics:Brain-to-body mass ratio|brain-to-body mass ratio]] is taken into account, the human brain is almost twice as large as that of a [[Biology:Bottlenose dolphin|bottlenose dolphin]], and three times as large as that of a [[Biology:Common chimpanzee|chimpanzee]]. However, a high ratio does not of itself demonstrate intelligence: very small animals have high ratios and the treeshrew has the largest quotient of any mammal.<ref>{{Cite web |url=http://genome.wustl.edu/genomes/view/tupaia_belangeri |title=Tupaia belangeri |publisher=The Genome Institute, Washington University |access-date=January 22, 2016 |url-status=live |archive-url=https://web.archive.org/web/20100601201841/http://genome.wustl.edu/genomes/view/tupaia_belangeri/ |archive-date=June 1, 2010  }}</ref>

===In popular culture===
[[File:PhrenologyPix.jpg|thumb|upright|[[Philosophy:Phrenology|Phrenology]] summarised in an 1883 chart]]

Earlier ideas about the relative importance of the different organs of the human body sometimes emphasised the heart.<ref>
{{cite book
 | last1 = Carrier
 | first1 = Martin
 | last2 = Mittelstrass
 | first2 = Jürgen
 | translator1-last = Lindberg
 | translator1-first = Steven
 | title = Mind, Brain, Behavior: The Mind-body Problem and the Philosophy of Psychology
 | year = 1991
 | trans-title = Geist, Gehirn, Verhalten
 | url = https://books.google.com/books?id=i7b7KgzRbJQC
 | edition = revised and expanded English
 | location = Berlin
 | publisher = Walter de Gruyter
 | publication-date = 1991
 | page = 11
 | isbn = 9783110128765
 | access-date = 22 May 2021
 | quote = [...] the Aristotelian view that the soul resides primarily in the heart [...].
}}
</ref>
Modern Western popular conceptions, in contrast, have placed increasing focus on the brain.<ref>
{{cite book
 | last1 = Cobb
 | first1 = Matthew
 | title = The Idea of the Brain: The Past and Future of Neuroscience
 | date = April 21, 2020
 | url = https://books.google.com/books?id=VVmqDwAAQBAJ
 | location = New York
 | publisher = Hachette UK
 | publication-date = 2020
 | isbn = 9781541646865
 | access-date = 22 May 2021
 | quote = [...] the ways in which we think about [the brain] are much richer than in the past, not simply because of the amazing facts we have discovered, but above all because of how we interpret them.
}}
</ref>

Research has disproved some common misconceptions about the brain. These include both ancient and modern myths. It is not true (for example) that neurons are not replaced after the age of two; nor that normal humans use only [[Biology:Ten percent of the brain myth|ten per cent of the brain]].<ref>{{cite book |last1=Jarrett |first1=C. |title=Great Myths of the Brain |publisher= John Wiley & Sons |isbn=978-1-118-31271-1 |url= https://books.google.com/books?id=fBPyBQAAQBAJ |date=November 17, 2014 }}</ref> Popular culture has also oversimplified the [[Biology:Lateralization of brain function|lateralisation of the brain]] by suggesting that functions are completely specific to one side of the brain or the other. Akio Mori coined the term "[[Unsolved:Game brain|game brain]]" for the unreliably supported theory that spending long periods playing [[Engineering:Video game|video game]]s harmed the brain's pre-frontal region, and impaired the expression of emotion and creativity.<ref>{{cite magazine|url= https://www.newscientist.com/article/dn2538-video-game-brain-damage-claim-criticised.html|title= Video game "brain damage" claim criticised|access-date=February 6, 2008|first=Helen |last= Phillips |date= July 11, 2002|magazine=New Scientist |url-status=live|archive-url= https://web.archive.org/web/20090111065557/http://www.newscientist.com/article/dn2538-video-game-brain-damage-claim-criticised.html|archive-date=January 11, 2009}}</ref>

Historically, particularly in the early-19th century, the brain featured in popular culture through [[Philosophy:Phrenology|phrenology]], a [[Unsolved:Pseudoscience|pseudoscience]] that assigned personality attributes to different regions of the cortex. The cortex remains important in popular culture as covered in books and satire.<ref>{{cite news |last1=Popova |first1=Maria |title='Brain Culture': How Neuroscience Became a Pop Culture Fixation |url=https://www.theatlantic.com/health/archive/2011/08/brain-culture-how-neuroscience-became-a-pop-culture-fixation/243810/ |work=The Atlantic |date=August 18, 2011 |url-status= live |archive-url= https://web.archive.org/web/20170728165041/https://www.theatlantic.com/health/archive/2011/08/brain-culture-how-neuroscience-became-a-pop-culture-fixation/243810/ |archive-date=July 28, 2017 }}</ref><ref>{{cite book |last1=Thornton |first1=Davi Johnson |title= Brain Culture. Neuroscience and Popular Media |date=2011 |publisher=Rutgers University Press |isbn=978-0-8135-5013-8}}</ref>

The human brain can feature in science fiction, with themes such as [[Engineering:Brain transplant|brain transplant]]s and cyborgs (beings with features like partly [[Philosophy:Artificial brain|artificial brain]]s).<ref>[http://web.mit.edu/digitalapollo/Documents/Chapter1/cyborgs.pdf Cyborgs and Space] {{webarchive|url= https://web.archive.org/web/20111006190955/http://web.mit.edu/digitalapollo/Documents/Chapter1/cyborgs.pdf |date=October 6, 2011 }}, in ''Astronautics'' (September 1960), by Manfred E. Clynes and Nathan S. Kline.</ref> The 1942 science-fiction book (adapted three times for the cinema) ''Donovan's Brain'' tells the tale of an [[Isolated brain|isolated brain]] kept alive ''in vitro'', gradually taking over the personality of the book's protagonist.<ref>{{cite book |author=Bergfelder, Tim |title= International Adventures: German Popular Cinema and European Co-productions in the 1960s |url= https://books.google.com/books?id=B1Nj41yxvZkC&pg=PA129 |year=2005 |publisher=Berghahn Books |isbn= 978-1-57181-538-5 |page=129}}</ref>
<!--Highbrow, Egghead, Professor Branestawm, [[Philosophy:Absent-minded professor|Absent-minded professor]], -->

==History==

=== Early history ===
[[File:Hieroglyph brain.svg|thumb|right|upright=1.0|[[Engineering:Hieroglyph|Hieroglyph]] for the word "brain" ({{Circa|1700 BC}})]]
The Edwin Smith Papyrus, an ancient Egyptian medical treatise written in the 17th century BC, contains the earliest recorded reference to the brain. The [[Engineering:Hieroglyph|hieroglyph]] for brain, occurring eight times in this papyrus, describes the symptoms, diagnosis, and prognosis of two traumatic injuries to the head. The papyrus mentions the external surface of the brain, the effects of injury (including seizures and [[Medicine:Aphasia|aphasia]]), the meninges, and cerebrospinal fluid.<ref name=Kandel>{{cite book |  last=Kandel | first=ER |author2=Schwartz JH |author3=Jessell TM  | title=Principles of Neural Science | edition=4th | publisher=McGraw-Hill | location=New York | year=2000 | isbn=978-0-8385-7701-1| title-link=Principles of Neural Science }}</ref><ref name="Adelman">{{cite book |last1=Gross|first1=Charles G. |editor-first=George |editor-last=Adelman |title=Encyclopedia of neuroscience |date=1987 |publisher=Birkhäeuser |location=Boston |isbn=978-0-8176-3335-6 |pages=843–847 |edition=2. |url=http://www.princeton.edu/~cggross/Hist_Neurosci_Ency_neurosci.pdf |url-status=live |archive-url=https://web.archive.org/web/20130505044949/http://www.princeton.edu/~cggross/Hist_Neurosci_Ency_neurosci.pdf |archive-date=May 5, 2013  }}</ref>

In the fifth century BC, [[Biography:Alcmaeon of Croton|Alcmaeon of Croton]] in Magna Grecia, first considered the brain to be the [[Philosophy:Sensorium|seat of the mind]].<ref name="Adelman"/> Also in the fifth century BC in Athens, the unknown author of ''On the Sacred Disease'', a medical treatise which is part of the Hippocratic Corpus and traditionally attributed to [[Biography:Hippocrates|Hippocrates]], believed the brain to be the seat of intelligence. [[Biography:Aristotle|Aristotle]], in his [[Biology:Aristotle's biology|biology]] initially believed the heart to be the seat of [[Philosophy:Intelligence|intelligence]], and saw the brain as a cooling mechanism for the blood. He reasoned that humans are more rational than the beasts because, among other reasons, they have a larger brain to cool their hot-bloodedness.<ref name=Bear>{{cite book | last=Bear | first=M.F. |author2=B.W. Connors |author3=M.A. Paradiso | title=Neuroscience: Exploring the Brain | location=Baltimore | publisher=Lippincott | year=2001 | isbn=978-0-7817-3944-3}}</ref> Aristotle did describe the meninges and distinguished between the cerebrum and cerebellum.<ref>von Staden, p.157</ref>

Herophilus of Chalcedon in the fourth and third centuries BC distinguished the cerebrum and the cerebellum, and provided the first clear description of the [[Biology:Ventricular system|ventricles]]; and with Erasistratus of Ceos experimented on living brains. Their works are now mostly lost, and we know about their achievements due mostly to secondary sources. Some of their discoveries had to be re-discovered a millennium after their deaths.<ref name="Adelman"/> Anatomist physician [[Biography:Galen|Galen]] in the second century AD, during the time of the Roman Empire, dissected the brains of sheep, monkeys, dogs, and pigs. He concluded that, as the cerebellum was denser than the brain, it must control the [[Biology:Muscle|muscle]]s, while as the cerebrum was soft, it must be where the senses were processed. Galen further theorised that the brain functioned by movement of animal spirits through the ventricles.<ref name="Adelman"/><ref name=Bear/>

===Renaissance===
[[File:1543, Andreas Vesalius' Fabrica, Base Of The Brain.jpg|thumb|upright|Drawing of the base of the brain, from Andreas Vesalius's 1543 work ''De humani corporis fabrica'']]
[[File:View of a Skull.jpg|thumb|upright|One of [[Biography:Leonardo da Vinci|Leonardo da Vinci]]'s sketches of the human skull]]
In 1316, Mondino de Luzzi's ''Anathomia'' began the modern study of brain anatomy.<ref>{{cite book |last1=Swanson |first1=Larry W. |title=Neuroanatomical Terminology: A Lexicon of Classical Origins and Historical Foundations |publisher=Oxford University Press |isbn=978-0-19-534062-4 |url=https://books.google.com/books?id=--PRAwAAQBAJ&q=nervous+system+anatomy+stagnation+galen+to+vesalius&pg=PA7|date=August 12, 2014 }}</ref>
Niccolò Massa discovered in 1536 that the ventricles were filled with fluid.<ref name=LOKHORST2016/> Archangelo Piccolomini of [[Place:Rome|Rome]] was the first to distinguish between the cerebrum and cerebral cortex.<ref name="Gross1999" /> In 1543 Andreas Vesalius published his seven-volume ''De humani corporis fabrica''.<ref name="Gross1999" /><ref name="MARSHALL">{{cite book |last1=Marshall |first1=Louise H. |last2=Magoun |first2=Horace W. |title=Discoveries in the Human Brain: Neuroscience Prehistory, Brain Structure, and Function |publisher=Springer Science & Business Media |isbn=978-1-475-74997-7 |page=44 |url=https://books.google.com/books?id=guncBwAAQBAJ&q=vesalius&pg=PR5|date=March 9, 2013 }}</ref><ref>{{cite book |last1=Holtz |first1=Anders |last2=Levi |first2=Richard |title=Spinal Cord Injury |publisher=Oxford University Press |isbn=978-0-19-970681-5 |url=https://books.google.com/books?id=ZvCqdwWwGRsC&pg=PA5|date=July 20, 2010 }}</ref> The seventh book covered the brain and eye, with detailed images of the ventricles, cranial nerves, [[Medicine:Pituitary gland|pituitary gland]], meninges, structures of the [[Biology:Human eye|eye]], the vascular supply to the brain and spinal cord, and an image of the peripheral nerves.<ref name="tessman">{{cite journal | author=Tessman, Patrick A. | author2=Suarez, Jose I. | year=2002 | title=Influence of early printmaking on the development of neuroanatomy and neurology | journal=Archives of Neurology | volume=59 | issue=12 | pages=1964–1969 | pmid=12470188 | doi=10.1001/archneur.59.12.1964 }}</ref> Vesalius rejected the common belief that the ventricles were responsible for brain function, arguing that many animals have a similar ventricular system to humans, but no true intelligence.<ref name="Gross1999">{{cite book |last1=Gross |first1=Charles G. |title=Brain, vision, memory : tales in the history of neuroscience. |date=1999 |publisher=MIT |location=Cambridge, Mass. |isbn=978-0-262-57135-7 |pages=37–51 |edition=1st MIT Press pbk.}}</ref>

[[Biography:René Descartes|René Descartes]] proposed the theory of dualism to tackle the issue of the brain's relation to the mind. He suggested that the [[Biology:Pineal gland|pineal gland]] was where the mind interacted with the body, serving as the seat of the soul and as the connection through which [[Philosophy:Animism|animal spirits]] passed from the blood into the brain.<ref name=LOKHORST2016>{{cite web |last1=Lokhorst |first1=Gert-Jan |title=Descartes and the Pineal Gland |url=https://plato.stanford.edu/entries/pineal-gland/ |website=The Stanford Encyclopedia of Philosophy |publisher=Metaphysics Research Lab, Stanford University |access-date=March 11, 2017 |date=January 1, 2016}}</ref> This dualism likely provided impetus for later anatomists to further explore the relationship between the anatomical and functional aspects of brain anatomy.<ref name=OCONNOR2003>{{cite journal |last1=O'Connor |first1=James |title=Thomas Willis and the background to Cerebri Anatome |journal=Journal of the Royal Society of Medicine |date=2003 |volume=96 |issue=3 |pages=139–143 |pmc=539424 |pmid=12612118 |doi=10.1177/014107680309600311}}</ref>

Thomas Willis is considered a second pioneer in the study of neurology and brain science. He wrote ''Cerebri Anatome'' ({{lang-la |Anatomy of the brain}}){{efn|Illustrated by architect Christopher Wren<ref name="Gross1999" />}} in 1664, followed by ''Cerebral Pathology'' in 1667. In these he described the structure of the cerebellum, the ventricles, the cerebral hemispheres, the brainstem, and the cranial nerves, studied its blood supply; and proposed functions associated with different areas of the brain.<ref name="Gross1999" /> The circle of Willis was named after his investigations into the blood supply of the brain, and he was the first to use the word "neurology."<ref name="Emery2000">{{cite journal |last1=EMERY |first1=ALAN |title=A Short History of Neurology: The British Contribution 1660–1910. Edited by F. CLIFFORD ROSE. (Pp. 282; illustrated; £25 Paperback; ISBN 07506 4165 7.) Oxford: Butterworth-Heinemann |journal=Journal of Anatomy |date=October 2000 |volume=197 |issue=3 |pages=513–518 |doi=10.1046/j.1469-7580.2000.197305131.x|pmc=1468164 }}</ref> Willis removed the brain from the body when examining it, and rejected the commonly held view that the cortex only consisted of blood vessels, and the view of the last two millennia that the cortex was only incidentally important.<ref name="Gross1999" />

<!--Early physiology-->In the middle of 19th century [[Biography:Emil du Bois-Reymond|Emil du Bois-Reymond]] and [[Biography:Hermann von Helmholtz|Hermann von Helmholtz]] were able to use a [[Engineering:Galvanometer|galvanometer]] to show that electrical impulses passed at measurable speeds along nerves, refuting the view of their teacher Johannes Peter Müller that the nerve impulse was a vital function that could not be measured.<ref>{{Cite journal |last1=Olesko |first1=Kathryn M. |last2=Holmes |first2=Frederic L. |date=1994 |editor-last=Cahan |editor-first=David |title=Experiment, Quantification, and Discovery: Helmholtz's Early Physiological Researches, 1843-50 |journal= |publisher=University of California Press |publication-place=Berkeley; Los Angeles; London |volume=Hermann von Helmholtz and the Foundations of Nineteenth Century Science |pages=50–108}}</ref><ref>{{cite web |last1=Sabbatini |first1=Renato M.E. |title=Sabbatini, R.M.E.: The Discovery of Bioelectricity. Nerve Conduction |url=http://www.cerebromente.org.br/n06/historia/bioelectr3_i.htm |website=www.cerebromente.org.br |access-date=June 10, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170626011707/http://www.cerebromente.org.br/n06/historia/bioelectr3_i.htm |archive-date=June 26, 2017  }}</ref><ref>{{Cite book |last=Finkelstein |first=Gabriel Ward |url=https://www.worldcat.org/oclc/864592470 |title=Emil du Bois-Reymond : neuroscience, self, and society in nineteenth-century Germany |date=2013 |isbn=978-1-4619-5032-5 |location=Cambridge, Massachusetts |oclc=864592470}}</ref> Richard Caton in 1875 demonstrated electrical impulses in the cerebral hemispheres of rabbits and monkeys.<ref>{{cite journal |last1=Karbowski |first1=Kazimierz |title=Sixty Years of Clinical Electroencephalography |journal=European Neurology |date=February 14, 2008 |volume=30 |issue=3 |pages=170–175 |doi=10.1159/000117338|pmid=2192889 }}</ref> In the 1820s, Jean Pierre Flourens pioneered the experimental method of damaging specific parts of animal brains describing the effects on movement and behavior.<ref>{{cite journal |last1=Pearce |first1=J.M.S. |title=Marie-Jean-Pierre Flourens (1794–1867) and Cortical Localization |journal=European Neurology |date=March 17, 2009 |volume=61 |issue=5 |pages=311–314 |doi=10.1159/000206858|pmid=19295220 |doi-access=free }}</ref>

===Modern period===
{{Further |Biology:Neuropsychiatry}}
[[File:Golgi 1885 Plate XXII.JPG|thumb|upright|Drawing by Camillo Golgi of vertical section of rabbit hippocampus, from his "Sulla fina anatomia degli organi centrali del sistema nervoso", 1885]]
[[File:CajalCerebellum.jpg|thumb|Drawing of cells in chick cerebellum by Santiago Ramón y Cajal, from "Estructura de los centros nerviosos de las aves", Madrid, 1905]]
<!--Neuronal doctrine-->Studies of the brain became more sophisticated with the use of the [[Engineering:Microscope|microscope]] and the development of a [[Chemistry:Silver stain|silver stain]]ing method by [[Biography:Camillo Golgi|Camillo Golgi]] during the 1880s. This was able to show the intricate structures of single neurons.<ref name="DECARLOS2007">{{cite journal |last1=De Carlos |first1=Juan A. |last2=Borrell |first2=José |title=A historical reflection of the contributions of Cajal and Golgi to the foundations of neuroscience |journal=Brain Research Reviews |date=August 2007 |volume=55 |issue=1 |pages=8–16 |doi=10.1016/j.brainresrev.2007.03.010|pmid=17490748 |hdl=10261/62299 |s2cid=7266966 |hdl-access=free }}</ref> This was used by [[Biography:Santiago Ramón y Cajal|Santiago Ramón y Cajal]] and led to the formation of the [[Biology:Neuron doctrine|neuron doctrine]], the then revolutionary hypothesis that the neuron is the functional unit of the brain. He used microscopy to uncover many cell types, and proposed functions for the cells he saw.<ref name="DECARLOS2007" /> For this, Golgi and Cajal are considered the founders of twentieth century neuroscience, both sharing the Nobel prize in 1906 for their studies and discoveries in this field.<ref name="DECARLOS2007" />

<!--Neuroscience-->[[Biography:Charles Scott Sherrington|Charles Sherrington]] published his influential 1906 work ''The Integrative Action of the Nervous System'' examining the function of reflexes, evolutionary development of the nervous system, functional specialisation of the brain, and layout and cellular function of the central nervous system.<ref>{{cite journal | last1=Burke | first1=R.E. | title=Sir Charles Sherrington's The integrative action of the nervous system: a centenary appreciation | journal=Brain | volume=130 | issue= Pt 4| pages=887–894 | doi=10.1093/brain/awm022 | pmid=17438014 | date=April 2007 | df=mdy-all | doi-access=free }}</ref> In 1942 he coined the term ''[[Philosophy:Enchanted loom|enchanted loom]]'' as a metaphor for the brain. [[Biography:John Farquhar Fulton|John Farquhar Fulton]], founded the ''Journal of Neurophysiology'' and published the first comprehensive textbook on the physiology of the nervous system during 1938.<ref name="SQUIRE1996">{{cite book |editor1-last=Squire |editor1-first=Larry R. |title=The history of neuroscience in autobiography |date=1996 |publisher=Society for Neuroscience |location=Washington DC |isbn=978-0-12-660305-7 |pages=475–97}}</ref> Neuroscience during the twentieth century began to be recognised as a distinct unified academic discipline, with David Rioch, Francis O. Schmitt, and Stephen Kuffler playing critical roles in establishing the field.<ref name="COWAN2000">{{Cite journal |last1=Cowan |first1=W.M. |last2=Harter |first2=D.H. |last3=Kandel |first3=E.R. |date=2000 |title=The emergence of modern neuroscience: Some implications for neurology and psychiatry |journal=Annual Review of Neuroscience |volume=23 |pages=345–346 |doi=10.1146/annurev.neuro.23.1.343 |pmid=10845068}}</ref> Rioch originated the integration of basic anatomical and physiological research with clinical psychiatry at the Walter Reed Army Institute of Research, starting in the 1950s.<ref>{{cite book |last1=Brady |first1=Joseph V. |last2=Nauta |first2=Walle J. H. |title=Principles, Practices, and Positions in Neuropsychiatric Research: Proceedings of a Conference Held in June 1970 at the Walter Reed Army Institute of Research, Washington, D.C., in Tribute to Dr. David Mckenzie Rioch upon His Retirement as Director of the Neuropsychiatry Division of That Institute |publisher=Elsevier |isbn=978-1-4831-5453-4 |page=vii |url=https://books.google.com/books?id=AK4aAwAAQBAJ&pg=PR7 |date=October 22, 2013 }}</ref> During the same period, Schmitt established the Neuroscience Research Program, an inter-university and international organisation, bringing together biology, medicine, psychological and behavioural sciences. The word neuroscience itself arises from this program.<ref>{{cite journal |last1=Adelman |first1=George |title=The Neurosciences Research Program at MIT and the Beginning of the Modern Field of Neuroscience |journal=Journal of the History of the Neurosciences |date=January 15, 2010 |volume=19 |issue=1 |pages=15–23 |doi=10.1080/09647040902720651|pmid=20391098 |s2cid=21513317 }}</ref>

Paul Broca associated regions of the brain with specific functions, in particular language in [[Biology:Broca's area|Broca's area]], following work on brain-damaged patients.<ref name="Neural Science 2000">Principles of Neural Science, 4th ed. Eric R. Kandel, James H. Schwartz, Thomas M. Jessel, eds. McGraw-Hill:New York, NY. 2000.</ref> John Hughlings Jackson described the function of the [[Biology:Motor cortex|motor cortex]] by watching the progression of epileptic seizures through the body. Carl Wernicke described [[Biology:Wernicke's area|a region]] associated with language comprehension and production. Korbinian Brodmann divided regions of the brain based on the appearance of cells.<ref name="Neural Science 2000" /> By 1950, Sherrington, Papez, and MacLean had identified many of the brainstem and limbic system functions.<ref name="Papez">{{cite journal |last1=Papez |first1=J.W. |title=A proposed mechanism of emotion. 1937. |journal=The Journal of Neuropsychiatry and Clinical Neurosciences |date=February 1995 |volume=7 |issue=1 |pages=103–12 |pmid=7711480 |doi=10.1176/jnp.7.1.103}}</ref><ref>{{cite journal |last1=Lambert |first1=Kelly G. |title=The life and career of Paul MacLean |journal=Physiology & Behavior |date=August 2003 |volume=79 |issue=3 |pages=343–349 |doi=10.1016/S0031-9384(03)00147-1|pmid=12954429 |s2cid=18596574 }}</ref> The capacity of the brain to re-organise and change with age, and a recognised critical development period, were attributed to [[Biology:Neuroplasticity|neuroplasticity]], pioneered by [[Biography:Margaret Kennard|Margaret Kennard]], who experimented on monkeys during the 1930-40s.<ref>{{cite book |last1=Chatterjee |first1=Anjan |last2=Coslett |first2=H. Branch |title=The Roots of Cognitive Neuroscience: Behavioral Neurology and Neuropsychology |publisher=OUP USA |isbn=978-0-19-539554-9 |pages=337–8 |url=https://books.google.com/books?id=f9dMAgAAQBAJ&q=neuroscience+20th+century&pg=PA338|date=December 2013 }}</ref>

<!--Neurosurgery-->Harvey Cushing (1869–1939) is recognised as the first proficient [[Medicine:Neurosurgery|brain surgeon]] in the world.<ref name="M.Bliss">{{cite book |url=https://books.google.com/books?id=EzbjVnjwjPYC |last=Bliss |first=Michael |title=Harvey Cushing : A Life in Surgery: A Life in Surgery |pages=ix–x |publisher=Oxford University Press |location=USA |date=October 1, 2005|isbn=978-0-19-534695-4 }}</ref> In 1937, Walter Dandy began the practice of vascular [[Medicine:Neurosurgery|neurosurgery]] by performing the first surgical clipping of an [[Medicine:Intracranial aneurysm|intracranial aneurysm]].<ref>{{cite journal | last1=Kretzer | first1=RM | last2=Coon | first2=AL | last3=Tamargo | first3=RJ | date=June 2010 | title=Walter E. Dandy's contributions to vascular neurosurgery | journal=Journal of Neurosurgery | volume=112 | issue=6 | pages=1182–91 | doi=10.3171/2009.7.JNS09737 | pmid=20515365 }}</ref>

==Comparative anatomy==
The human brain has many properties that are common to all [[Biology:Vertebrate|vertebrate]] brains.<ref>{{cite book |last1=Glees |first1=Paul |title=The Human Brain |date=2005 |publisher=Cambridge University Press |isbn=978-0-521-01781-7 |page=1 |url=https://books.google.com/books?id=kWgeOPGdl_MC&pg=PA1}}</ref> Many of its features are common to all [[Biology:Mammal|mammal]]ian brains,<ref name="Simpkins">{{cite book |first1=C. Alexander |last1=Simpkins |first2=Annellen M. |last2=Simpkins |title=Neuroscience for Clinicians: Evidence, Models, and Practice |isbn=978-1-4614-4842-6 |publisher=Springer Science & Business Media |year=2012 |page=143 |url=https://books.google.com/books?id=QG4LC-d2sm8C&pg=PA143}}</ref> most notably a six-layered cerebral cortex and a set of associated structures,<ref name="Bornstein">{{cite book |first1=Marc H. |last1=Bornstein |first2=Michael E. |last2=Lamb |title=Developmental Science: An Advanced Textbook |isbn=978-1-136-28220-1 |publisher=Psychology Press |year=2015 |page=220 |url=https://books.google.com/books?id=XhA-CgAAQBAJ&pg=PA220}}</ref> including the hippocampus and [[Medicine:Amygdala|amygdala]].<ref name="Bernstein">{{cite book |first=Douglas |last=Bernstein |title=Essentials of Psychology |isbn=978-0-495-90693-3 |publisher=Cengage Learning |year=2010 |page=64 |url=https://books.google.com/books?id=rd77N0KsLVkC&pg=PA64}}</ref> The cortex is proportionally larger in humans than in many other mammals.<ref name="HOFMAN2014">{{cite journal |last1=Hofman |first1=Michel A. |title=Evolution of the human brain: when bigger is better |journal=Frontiers in Neuroanatomy |date=March 27, 2014 |volume=8 |page=15 |doi=10.3389/fnana.2014.00015|pmid=24723857 |pmc=3973910 |doi-access=free }}</ref> Humans have more association cortex, sensory and motor parts than smaller mammals such as the rat and the cat.<ref>{{Cite book |title=Psychology |last=Gray |first=Peter |publisher=Worth Publishers |year=2002 |isbn=978-0-7167-5162-5 |edition=4th |oclc=46640860 |url=https://archive.org/details/psychology00gray }}</ref>

As a [[Biology:Primate|primate]] brain, the human brain has a much larger cerebral cortex, in proportion to body size, than most mammals,<ref name="Bernstein" /> and a highly developed visual system.<ref name="Lu">{{cite book |url=https://books.google.com/books?id=nYr6AQAAQBAJ&pg=PA3 |title=Visual Psychophysics: From Laboratory to Theory |publisher=MIT Press |year=2013 |isbn=978-0-262-01945-3 |page=3 |last1=Lu |first1=Zhong-Lin |last2=Dosher |first2=Barbara  }}</ref><ref name="Sharwood Smith">{{cite book |url=https://books.google.com/books?id=fe-SDQAAQBAJ&pg=PA206 |title=Introducing Language and Cognition |publisher={{wipe|Cambridge University Press}} |year=2017 |isbn=978-1-107-15289-2 |page=206 |first=Mike |last=Sharwood Smith}}</ref>

As a [[Biology:Hominidae|hominid]] brain, the human brain is substantially enlarged even in comparison to the brain of a typical monkey. The sequence of [[Biology:Human evolution|human evolution]] from ''[[Biology:Australopithecus|Australopithecus]]'' (four million years ago) to [[Biology:Human|''Homo sapiens'']] (modern humans) was marked by a steady increase in brain size.<ref name="Kolb and Whishaw">{{cite book |last1=Kolb |first1=Bryan |last2=Whishaw |first2=Ian Q. |title=Introduction to Brain and Behavior |publisher=Macmillan Higher Education |isbn=978-1-4641-3960-4 |page=21 |year=2013 |url=https://books.google.com/books?id=teUkAAAAQBAJ}}</ref><ref name="Nieuwenhuys">{{cite book |last1=Nieuwenhuys |first1=Rudolf |last2=ten Donkelaar |first2=Hans J. |last3=Nicholson |first3=Charles  |title=The Central Nervous System of Vertebrates |publisher=[[Company:Springer Science+Business Media|Springer]] |isbn=978-3-642-18262-4 |page=2127 |year=2014 |url=https://books.google.com/books?id=gsDqCAAAQBAJ&pg=PA2127}}</ref> As brain size increased, this altered the size and shape of the skull,<ref name="Lee Lerner">{{cite book |last1=Lerner |first1=Lee |last2=Lerner |first2=Brenda Wilmoth |title=The Gale Encyclopedia of Science: Pheasants-Star |isbn=978-0-7876-7559-2 |publisher=[[Company:Gale (publisher)|Gale]] |year=2004 |page=3759 |url=https://books.google.com/books?id=mp7kcdK6SekC |quote=As human's position changed and the manner in which the skull balanced on the spinal column pivoted, the brain expanded, altering the shape of the cranium.}}</ref> from about 600 [[Cubic centimetre|cm<sup>3</sup>]] in ''[[Biology:Homo habilis|Homo habilis]]'' to an average of about 1520&nbsp;cm<sup>3</sup> in ''Homo neanderthalensis''.<ref>{{cite book |last1=Begun |first1=David R. |title=A Companion to Paleoanthropology |date=2012 |publisher=John Wiley & Sons |isbn=978-1-118-33237-5 |page=388 |url=https://books.google.com/books?id=oIoT1RcFeCwC&pg=PT388}}</ref> Differences in [[Biology:DNA|DNA]], [[Biology:Gene expression|gene expression]], and [[Philosophy:Gene–environment interaction|gene–environment interaction]]s help explain the differences between the function of the human brain and other primates.<ref>{{cite journal |author=Jones, R. |title=Neurogenetics: What makes a human brain? |journal=Nature Reviews Neuroscience |volume=13 |page=655 |year=2012 |pmid=22992645 |doi=10.1038/nrn3355 |issue=10|s2cid=44421363 |doi-access=free }}</ref>

== See also ==
*Cerebral atrophy
*[[Biology:Cortical spreading depression|Cortical spreading depression]]
*[[Philosophy:Evolution of human intelligence|Evolution of human intelligence]]
*[[Biology:Large-scale brain networks|Large-scale brain networks]]
*[[Biology:Outline of neuroscience|Outline of neuroscience]]
*Superficial veins of the brain

==References==
{{Reflist}}

==Bibliography==
* {{cite book |<!--"Davidson's"-->editor1-first=Nicki R. |editor1-last=Colledge |editor2-first=Brian R. |editor2-last=Walker |editor3-first=Stuart H. |editor3-last=Ralston |editor4-last=Ralston |title=Davidson's Principles and Practice of Medicine |date=2010 |publisher=Churchill Livingstone/Elsevier |location=Edinburgh |isbn=978-0-7020-3085-7 |edition=21st |ref={{harvid |Davidson's|2010}}}}
* {{cite book |<!--"Guyton & Hall"-->last1=Hall |first1=John |title=Guyton and Hall Textbook of Medical Physiology |year=2011 |publisher=Saunders/Elsevier |location=Philadelphia, PA |isbn=978-1-4160-4574-8 |edition=12th |ref={{harvid |Guyton & Hall|2011}}}}
* {{cite book |<!--"Larsen"-->last1=Larsen |first1=William J. |title=Human Embryology |date=2001 |publisher=Churchill Livingstone |location=Philadelphia, PA |isbn=978-0-443-06583-5 |edition=3rd }}
* {{cite book |<!--"Elsevier's"-->last2=Ort |first1=Bruce Ian |last1=Bogart |first2=Victoria |title=Elsevier's Integrated Anatomy and Embryology |date=2007 |publisher=Elsevier Saunders |location=Philadelphia, PA |isbn=978-1-4160-3165-9 |ref={{harvid |Elsevier's|2007}}}}
* {{cite book |<!--"Pocock"-->last1=Pocock |first1=G. |last2=Richards |first2=C. |title=Human Physiology: The Basis of Medicine |date=2006 |publisher=Oxford University Press |location=Oxford |isbn=978-0-19-856878-0 |edition=3rd |ref={{harvid |Pocock|2006}}}}
* {{cite book |<!--"Purves"-->last1=Purves |first1=Dale |title=Neuroscience |date=2012 |publisher=Sinauer associates |location=Sunderland, MA |isbn=978-0-87893-695-3 |edition=5th }}
* {{cite book |<!--"Squire"-->last1=Squire |first1=Larry |title=Fundamental Neuroscience |date=2013 |publisher=Elsevier |location=Waltham, MA |isbn=978-0-12-385870-2 }}
* {{cite book |<!--"Gray's Anatomy"-->editor1-last=Standring |editor1-first=Susan |title=Gray's Anatomy: The Anatomical Basis of Clinical Practice |date=2008 |publisher=Churchill Livingstone |location=London |isbn=978-0-8089-2371-8 |edition=40th |ref={{harvid |Gray's Anatomy|2008}}}}

==Notes==
{{Notelist}}

==External links==
* [http://faculty.washington.edu/chudler/facts.html Brain facts and figures] – Washington.edu
*[https://web.archive.org/web/20210301111048/https://www.nationalgeographic.com/science/article/brain-2 Human brain] – National Geographic

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{{Human systems and organs}}
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[[Category:Brain anatomy]]

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