Human brain

• 1. Introduction

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  The human brain has the consistency of soft tofu, and yet it holds an estimated 86 billion neurons. That gel-like organ sits at the centre of the nervous system and, together with the spinal cord, forms the central nervous system. It takes in sensory information, weighs it, and sends out instructions that run most of what the body does.

  How does something so soft produce planning, language, fear, and memory? What keeps it alive, and what shields it from the rest of the body? Why does the left side of the brain steer the right hand? And why, after centuries of philosophy and decades of imaging, do researchers still say the brain is not fully understood?

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• 2. Architecture

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  A deep groove called the longitudinal fissure divides the cerebrum, the largest part of the brain, into two nearly symmetrical hemispheres. Five commissures span that groove, and the biggest of them is the corpus callosum. Each hemisphere is conventionally split into four lobes: frontal, parietal, temporal, and occipital. They are named after the skull bones lying over them. The frontal lobe handles attention, abstract thinking, problem-solving, and personality, and it also holds Broca's area for speech. The occipital lobe is the smallest and deals with vision and colour recognition. The temporal lobe is tied to auditory and visual memories and to language. Some sources add a central lobe, a limbic lobe, and an insular lobe.

  The surface of the cerebrum is folded into ridges called gyri and grooves called sulci. The cortex, the outer layer of grey matter, is only 2 to 4 mm thick. Most of it is neocortex with six layers of neurons, while the older allocortex has three or four. Under a microscope the cortex divides into about fifty distinct zones known as Brodmann's areas. The primary motor cortex sits at the rear of the frontal lobe, directly in front of the somatosensory area. The remaining cortex, called association areas, takes input from the senses and from lower brain regions for perception, thought, and decision-making.

  Beneath the cortex lies white matter, which makes up about half of the total brain volume. The whole brain measures around 1260 cm3 in men and 1130 cm3 in women. Deep inside the hemispheres sit the basal ganglia, which help regulate behaviour and movement. The largest of them is the striatum. Between the insular cortex and the striatum lies the claustrum, a thin sheet of neurons. Nearby, the basal forebrain structures produce acetylcholine and distribute it widely.

  Behind the brainstem sits the cerebellum, whose name means little brain. It has an anterior lobe, a posterior lobe, and a flocculonodular lobe, and a central strip called the vermis joins the first two. Three pairs of nerve tracts called cerebellar peduncles tether it to the brainstem. The anterior and posterior lobes appear to smooth and coordinate complex movements, while the flocculonodular lobe helps maintain balance. The brainstem itself consists of the midbrain, the pons, and the medulla. Ten of the twelve pairs of cranial nerves leave directly from it. Where the brainstem exits the skull through a large opening in the occipital bone called the foramen magnum, the spinal cord begins.

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• 3. Protection and Plumbing

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  Three membranes called meninges wrap the cerebrum, brainstem, cerebellum, and spinal cord. The outer one is the tough dura mater, the middle one is the arachnoid mater, and the delicate inner one is the pia mater. Cerebrospinal fluid fills the subarachnoid space between the last two. In 2023 a fourth layer was proposed, named the subarachnoid lymphatic-like membrane.

  At any moment the body holds about 150 mL of cerebrospinal fluid, most of it in that subarachnoid space. The fluid is replaced roughly once every 5-6 hours. It is made by the choroid plexus inside four ventricles: two lateral, a third, and a fourth. A single channel, the cerebral aqueduct, links the third ventricle to the fourth. From there three openings release the fluid into the cisterna magna, one of the major cisterns, and it flows around the brain and spinal cord.

  The circle of Willis is a ring of arteries lying between the midbrain and pons. It gathers blood from two sources. The internal carotid arteries feed the front of the brain, and the vertebral arteries, which climb through openings in the neck vertebrae, feed the back. The two vertebral arteries merge into the larger basilar artery, which later splits into two posterior cerebral arteries. On the way out, deoxygenated blood drains into dural venous sinuses. The large superior sagittal sinus on top of the brain eventually empties, through the transverse and sigmoid sinuses, into the internal jugular veins.

  The smallest vessels in the brain are lined with cells joined by tight junctions, and pericytes play a major role in forming them. Fluids therefore seep across far less than in capillaries elsewhere. This is the blood-brain barrier. Water, carbon dioxide, oxygen, and fat-soluble substances such as anaesthetics and alcohol still pass through it. The barrier is absent in circumventricular organs, including the pineal gland and the area postrema, because these structures must respond to changes in body fluids. The outermost layer of the cortex, the glia limitans, is built from the foot-like endings of astrocytes, a cell type with its own story.

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• 4. Cells, Signals, Fuel

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  Of the brain's neurons, 69 billion, about 80 percent, sit in the cerebellum, while only 16 billion, or 19 percent, are in the cerebral cortex. Non-neuronal cells are estimated at 85 billion, give or take 10 billion. Among the neurons are the Betz cells, whose cell bodies are the largest in the entire nervous system. Among the glial cells, astrocytes are the largest. They are star-shaped, with many processes radiating from the cell body. Roughly 400 of the genes expressed in the human body are specific to the brain, out of just under 20,000 protein-coding genes seen to be expressed.

  A neuron has a cell body, an axon, and branching dendrites. Dendrites collect signals from the axon terminals of other neurons. If those signals trigger an action potential, an electrochemical pulse starts at a specialised stretch of the axon and travels to its end. There it triggers the release of a neurotransmitter at a synapse. Dopamine, serotonin, GABA, glutamate, and acetylcholine are among the chemical messengers involved. GABA is the brain's major inhibitory transmitter and glutamate its major excitatory one. Linked neurons build circuits and large networks, such as the salience network and the default mode network.

  The brain makes up only 2 percent of body weight, yet it takes 15 percent of the cardiac output, 20 percent of the oxygen the body uses, and 25 percent of its glucose. In a fasted, sedentary person it uses approximately 60 percent of blood glucose. When glucose runs low, during fasting or endurance exercise, the brain switches to ketone bodies, and it can burn lactate during exercise. Long-chain fatty acids cannot cross the blood-brain barrier, but some short-chain and medium-chain fatty acids can. Active cortical regions burn slightly more energy than idle ones, and that difference underlies the PET and fMRI scans. A preliminary study suggests the brain's metabolic demand peaks at about five years old.

  The suprachiasmatic nucleus and the ventrolateral preoptic nucleus in the hypothalamus run a roughly 24 hour internal clock. Sleep is part of that rhythm, and its purpose is not fully understood. Evidence suggests that during sleep the brain clears out waste products, some of them potentially neurotoxic, and that it may also prune unnecessary connections. The clearing is credited to the glymphatic system, described as the brain's lymphatic drainage, with routes running alongside cerebral blood vessels.

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• 5. Building a Brain

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  At the start of the third week of development, the embryo's ectoderm thickens into a strip called the neural plate. By the fourth week the plate has widened at one end, and its edges, the neural folds, curl together to close into the neural tube. Neural crest cells are caught along its length, and the head end of the tube gives rise to the brain. The cerebral hemispheres first appear on day 32. Three swellings known as primary brain vesicles mark the future forebrain, midbrain, and hindbrain.

  In the fifth week these swellings multiply into five secondary vesicles. The telencephalon will give rise to the cerebral cortex and basal ganglia, and the diencephalon to the thalamus and hypothalamus. The metencephalon becomes the cerebellum and pons, and the myelencephalon becomes the medulla oblongata. In the same week the brain splits into repeating segments called neuromeres, known as rhombomeres in the hindbrain.

  For just over five months of prenatal life the cortex stays smooth. By 24 weeks of gestational age it has wrinkled enough to show the fissures that outline the lobes. Why the cortex folds is not well understood. Proposed explanations include mechanical buckling, tension in the axons, and differential tangential expansion. What is clear is that folding follows a pattern that is consistent between individuals and across most species. The first groove, the lateral cerebral fossa, appears in the fourth month. It deepens into the lateral sulcus, which marks out the temporal lobe. By the sixth month other sulci outline the frontal, parietal, and occipital lobes. A gene called ARHGAP11B may play a major part in this process.

  Pregnancy can disturb all of this. Nutritional deficiencies, teratogens, infections, and recreational drugs, including alcohol, can affect normal development, and alcohol may result in fetal alcohol spectrum disorders. A rare group of conditions called lissencephaly is marked by cortical folding that is missing or inadequate.

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• 6. Crossed Wires

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  The cerebrum is wired contralaterally, so the left hemisphere deals mainly with the right half of the body, and the right hemisphere with the left. A developmental axial twist is theorised to explain this. Motor and sensory connections both cross sides in the brainstem. Vision follows a more elaborate rule. At the optic chiasm, half of the fibres from each optic nerve switch sides. As a result, everything in the left half of the visual field ends up in the right half of the brain.

  The cortex gives some body parts far more territory than others. The hands and mouth claim much larger areas than other body parts, which allows finer movement, and a drawing of this uneven map is called a motor homunculus. Language is another asymmetry. The left frontal lobe is dominant for it. Damage to a key language area on the left can leave a person unable to speak or understand, whereas equivalent damage on the right causes only minor impairment. Language was traditionally pinned to Wernicke's area and Broca's area, but it is now mostly accepted that a wider network of cortical regions contributes.

  Much of what is known about cooperation between the two hemispheres comes from split-brain patients. These people had the corpus callosum surgically cut in an attempt to ease epileptic seizures. Their behaviour is not obviously unusual, but in some cases they act almost like two people in one body. One hand may take an action and the other hand may undo it. If a picture is briefly shown to the right of the point where they are looking, they can describe it aloud. If it is shown to the left, they cannot name it, though the left hand may still point to what the object was.

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• 7. When It Fails

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  A traumatic brain injury can come from contact sport, a fall, or a traffic or work accident. Immediate effects include bleeding inside the brain, bruising, a fractured skull, deafness, and concussion. Bruising can damage widespread nerve tracts, producing diffuse axonal injury. A blow may also harm the side opposite the impact, which is called a contrecoup injury. Longer-term problems include posttraumatic stress disorder and hydrocephalus. Chronic traumatic encephalopathy can develop after multiple head injuries.

  A stroke is a drop in blood supply to part of the brain, causing cell death. The FAST warning signs are facial droop, arm weakness, and speech difficulties. Trouble with movement, speech, or sight usually points to the cerebrum, while imbalance, double vision, and vertigo usually point to the brainstem or cerebellum. Transient ischaemic attacks are strokes whose symptoms resolve within 24 hours. Some treatments are time-critical, such as dissolving or surgically removing a clot, so hospitals speed up investigation with a CT scan. A history of stroke raises the risk of dementia by around 70 percent, and a recent stroke raises it by around 120 percent.

  Neurodegenerative diseases destroy neurons progressively and get worse with age. The common types include Alzheimer's disease, vascular dementia, alcoholic dementia, and Parkinson's disease dementia. Rarer ones include Huntington's disease and Wilson's disease. Prion diseases, including Creutzfeldt-Jakob disease and kuru, are fatal. Cerebral atherosclerosis, a build-up of cholesterol plaques in the large arteries of the brain, contributes to dementia. Viruses, bacteria, and fungi can infect the meninges as meningitis, the brain matter as encephalitis, or form an abscess inside it.

  Most malignant brain tumours begin elsewhere in the body, most commonly in the lung, breast, and skin. Meningioma, a cancer of the meninges, is more common than cancers of brain tissue itself. The corticosteroid dexamethasone is often given to reduce swelling around a tumour. Seizures are thought to reflect abnormal electrical activity, and status epilepticus means a seizure or series of seizures that has not ended within five minutes. At the far end sits brain death, an irreversible total loss of brain function marked by coma, loss of reflexes, and apnoea. Its declaration varies geographically and is not always accepted, and poor communication with the patient's family often makes the process harder.

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• 8. Studying the Mind

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  Gottfried Leibniz asked his readers to imagine a machine that could think, enlarged until a person could walk inside it like a windmill. In his Monadology he wrote that such a visitor would "find only parts pushing one another, and never anything by which to explain a perception." That doubt about mechanical explanations pushed René Descartes and many others toward dualism, the belief that the mind is partly independent of the brain.

  The railway worker Phineas Gage pushed the other way. In the 19th century, an iron rod passed through his brain, and his case convinced researchers and the public that cognitive functions are localised in the brain. The same century produced the pseudoscience of phrenology, which tried to assign personality traits to regions of the cortex. Today most neuroscientists and contemporary philosophers are materialists. Fiction has played with the idea too, as in the 1942 tale Donovan's Brain, which imagines a brain transplant.

  Bigger does not simply mean smarter. Studies find small to moderate correlations, averaging around 0.3 to 0.4, between brain volume and IQ. Whales and elephants have larger brains than humans. Compared with body mass, the human brain is almost twice as large as a bottlenose dolphin's and three times as large as a chimpanzee's. Even so, a high ratio alone proves nothing, because the treeshrew has the largest ratio of any mammal.

  Researchers use an electroencephalogram, with electrodes placed on the scalp, to record the cortex without surgery. Electrocorticography places electrodes directly on the exposed brain surface, and microelectrodes can record from a single neuron. Functional magnetic resonance imaging avoids the radioactive materials needed by SPECT and PET, and it offers higher resolution. Cerebral organoids now let scientists study how the brain and cortex grow. The Decade of the Brain, a United States initiative of the 1990s, helped drive a surge in research, and the BRAIN Initiative followed in 2013. The Human Connectome Project, a five-year study launched in 2009, mapped anatomical and functional connections. An emerging next phase may be simulating brain activity itself.

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