The brain is both an easy and difficult thing to define. In many ways there are three brains. The first, called the cerebrum, is what every one pictures. It is about three pounds, and composed of 20-30 billion neurons and synapsing with each other.

The second definition of the brain is the cerebellum. It too is a cortex. It is like a second small brain tucked behind the brain stem and under the cerebrum. The cerebellum has more neurons that the cerebrum but they are tiny and tightly compacted.

The third definition is that the brain is everything in the head. This includes the cerebellum, the cerebrum and everything under the cerebrum. In many ways this is the best definition because all of these parts work together.

Let’s take a quick tour of the brain’s development, structures and processes.

Cerebral Cortex

Cerebrum

The brain is an amazing structure. It varies across species in size and complexity. Some invertebrates don’t have brains (sponges, jellyfish and starfish). But most of us do have brains and are the better for it.

If you took pizza dough and rolled it out into a thin-crusted large pizza, folded it many times and stuck it in your head, you’d have one hemisphere of the cerebrum. A second large pizza of neurons would form the other hemisphere.

This neural pizza is about 2-3 dimes thick. The folds vary somewhat between people. They provide lots of surface area which is organized in a 2-D fashion (left and right more than in depth.

It is protected by skull bones and suspended in cerebrospinal fluid. The blood vessels in the cerebrum prevent most molecules (aside from oxygen and carbon dioxide) from easily passing into the brain cells. This blood-brain barrier works better in some parts of the brain than in others but it does help isolate the brain for the rest of the body’s diseases, usually.

This gray matter (non-insulated neurons) can be poisoned (alcohol), infected (rarely) and damaged both externally (head injuries) and internally (Parkinson’s and Alzheimer’s diseases. Some disorder seem to be related to brain development (such schizophrenia, ADHD, OCD) or neural processing (mood disorders, PTSD).

 

Development

The brain is not the first part of the body to development. The heart begins beating before almost everything else. A developing brain needs a good circulatory system.

The brain starts as a primitive streak. The steak flattens into a plate. The middle of the plate deepens into a grove. Cells from each side of the grove zip it up into a neural tube. The cells inside the tube become the cortex, the spinal cord and all the structures of the brainstem and limbic system.

At 18 days after conception, the outer layer on the back of the embryo thickens and forms a plate. The edges then curl up to make a neural tube. The cells inside tube become neurons & glial cells.

The tube forms 3 bulges, which will become the forebrain, midbrain and hindbrain. The forebrain will become the cerebral cortex and limbic system, including the basal ganglia, thalamus and hypothalamus. The midbrain will become  the superior colliculi (needed for vision), the inferior colliculi (used in hearing(, and small clusters of cells used for homeostasis and reflexes. The hindbrain becomes the medulla oblongata, cerebellum, and pons.

Development proceeds in two phases. First, systematic division occurs. Two identical founder cells are produced. Two so you get two ears, two eyes, and two cerebral hemisphere. These are radical glial cells which spread out (radiate) like a tree. Second, asymmetric development customizes regions for different functions.  About 3 months after fertilization, both founder cells and neurons are produced. The neurons climb the glial tree and find their respective spot. At the end of cortical development, founder cells die off, leaving the neurons behind.

When neurons reach home, they connect with each other. Failure to connect results in death. Neurons need other neurons. During development, synapses form randomly. But a sort of neural Darwinism occurs. Connection that are successful are kept. Synapses that ineffective disappear.As life continues, it is a constant process of forming synapses, eliminating them, and reestablishing connections. This  neuro-plasticity is a key feature of the brain. There is more plasticity when young but it never fully disappears.

Genetics has an indirect impact on us. It affects the hardware. Genetics determines how many brain cells there are, how well the blood vessels are constructed, and which nerves are myelinated. We can do a lot with software to compensate for hardware issues but hardware does set the limits.

Environmental factors play a role, and it is often hard to know it a condition is caused by genetics or prenatal environment.Even in finding their homes, radiating neurons avoid places inhospitable to their survival, and follow paths of similarity constructed neurons.

There are five stages of neural development. Proliferation is the first stages. New cells are produced. The cells along the ventricles divide to become neurons and glia. Stage two is migration. Primitive neurons find their homes. Chemicals guide them along the way.

Stage three is differentiation. Neurons get axons & dendrites, which makes them different from other cells.

Myelination is stage four. Glia cells produce myelin sheaths which insulate nerves, increasing their speed and preventing unwanted cross-stimulation. The process begins in the spinal cord, then the brain, ending at about age 30.

Synaptogenesis is the last stage, and it continues throughout life. It is the process of forming and re-forming synapses.

Neurons

At the most basic level, the body is run by neurons. These cells link together to provide sensory information and trigger muscle movements. Each neuron is a cell with all the regular functions. It’s cell body (soma) has a nucleus, DNA, RNA, mitochondria and all the standard cell components.

Neurons have some additional structure components and a very different functional component. Structurally, neurons typically come with extensions. The dendrites look like ginger covered with spiny bristles. Neurotransmitters bind to the receptors of the dendritic spines, so dendrites are important for inputs.

Neurons are amazing. Functionally, they are living batteries that discharge quickly, recharge and discharge again. There are factories to produce the needed components, tubes to carry products, and pumps and gates to manage its climate.

Summation (integration) is the process of connecting neurons together. Think of it as a wiring plan. Some neurons receive inputs from hundreds or thousands of other neurons. This allows signals to be summed. ‘It’s not cold until 50 other receptors tell me it is cold.”

Variations in the firing of input neurons make a summation neuron more of likely to accurately. Think of it as a committee vote. Lots of voters, one reporter. Each input either excites or inhibits firing. The likelihood of a summation neuron can be calculated by adding the excitatory post-synaptic potentials (EPSP) and the inhibitory post-synaptic potentials (IPSP) together.

 

Non-Neurons

The has three things in it: neurons, blood vessels and glia. Blood flow to the brain is essential for life. If the heart stops beating (heart attack), no blood reaches the brain, which means no oxygen, no glucose, and no removal oscwaste products.

Neurons are tiny combustion engines. If you remember your auto shop or camping classes, there are three things needed to make a fire:Nairobi, fuel and heat. There also has to be some place for the smoke of exhaust emissions to go. Neurons need air z9oxygen), and fuel (glucose) . Both are delivered by the blood. Heat is supplied by the ATP enzyme. Cat on dioxide is transferred back into the blood.

Glial cells are non-neuron cells that perform support functions. These neuroglia are sometimes called “neural glue,” because they keep the brain together. Let me highlight 6 types of glial cells. First, there are the radial glial cells previously mentioned. They radiate out to form a tree that the neurons can climb. Second, star-shaped astrocytes help stabilize synapses, re-uptake neurotransmitters, and help form the blood-brain barrier. Astrocytes hold neurons in place, provide nutrients and raw material, and engulf dead cells and form scar tissue.

The third type of glia are satellite cells. They are the astrocytes of the peripheral nervous system. They give support to neurons.

Types fourth and fifth types of glia insulate nerves by producing myelin. Oligodendrocytes make spots of myelin in the brain. Multiples axons can pass through them without touching each other. In contrast, Schwann cells myelinate nerves in the peripheral nervous system by wrapping around long axons. They look like TootsieRolls strung on a stick. Schwann cell, space, Schwann cell, space, etc.. The spaces are called Nodes of Ranvier.

The fifth type of glia is microglia, which are the smallest glial cells. They act as if they were phagocytes (bacteria eating white blood cells). It is their job to protect the brain from invading microorganisms.

 

Chemicals

Neurotransmitters

Your brain on drugs, naturally. “Just Say No” doesn’t apply to these drugs. Neurotransmitters are built-in drugs. You have to have them to make interconnections between neurons.

If the activity within a neuron is primarily electrical (though battery driven), the connections between neurons are typically chemical. Once a neuron’s depolarization reaches the terminal buttons, calcium channels are activated to release neurotransmitters into the synapse.

The primary neurotransmitter used in the brain is glutamate. It account for 90% of the connections. It is the GO signal for the brain, so it obviously will be high. The STOP signals come from GABA. It accounts for 9% of neural activity. We clearly are “go” driven. All of the hundreds of other neurotransmitters account for the remaining 1%.

Other Chemicals

Nerve growth factor (NGF) is important for neural survival, muscle growth and cell stabilization. If there is not enough NGF, axons degenerate and cell bodies die. Neurotrophin is similar to NGF. It helps promote cell survival and activity. BDNF is brain-derived neurotrophic factor. It is the most abundant neurotrophin in cortex.During development, it is used to stimulate axon and dendritic growth, but it is also used in adult brains. Deficiencies of any of these neurotrophins lead to cortical shrinking and brain diseases.

 

Hemispheres

The cerebral cortex has two hemispheres, situated laterally. They are separated by the longitudinal fissure but are connected by the corpus callosum. Each hemisphere is about the size of a large pizza folded multiple times and stuffed into the head.

The outside of the hemisphere is gray, layered on top of white matter (myelinated cells). Fissures are sulci (sulcus, singular), and ridges are gyri (gytus, singular). Given the folded structure there is a lot of surface area available. The hemispheres are mostly mirror images of each other, with the right one positioned slightly forward.

Most brain functions are distributed between the hemispheres. A good exception is language, which is typically in the opposite side of handedness. If you’re right handed, your language centers are probably in the other hemisphere.

Logic and storytelling typically go with language. In most people, then, it is the left hemisphere that tries to make sense of the world, filling gaps in knowledge, and generating hypotheses of what will happen next. Damage to the left hemisphere disrupts movement of the right side, makes it difficult to identify objects that are face-like, and interferes with language but doesn’t impact intonation.

The right hemisphere controls motor function of the left side, helps you identify the emotion of others, and tells you if you are looking at an actual face. Damage to  right hemisphere typicallyy results in incoherent relationships between objects, only recognizing parts of objects, and okay language with flat emotional intonation.

 

Lobes

The brain has four easily identifiable zones. Each is somewhat rounded, and performs specialized functions. All of the interconnect, transfer information and coordinate their functions. The brain has parts but it functions as a whole.

Occipital Lobe

There are eyes in the back of your head. Well, okay, not actual eyes. But at least there are vsion processors for the information that comes from the eyes. The occipital lobe is at the back of the head, just above the neck. This is the primary projection area for vision.

Sensory information comes from the eyes, passes through the LGN, reaches the occipital lobe, is processed and then routed to both the parietal and temporal lobes. The cortex here is striated into 6 layers. Each has its own speciality.

The processed visual information is distributed to both the parietal and temporal lobes. The dorsal path goes from the occipital lobe up to the parietal lobe to help give you a 3D view of the world. The ventral path goes along the side of the head to the temporal lobe where you keep your mental encyclopedia.

 

Temporal Lobe

The temporal lobe is critical for processing vision, memory and sound. It is sent information from the occipital lobe for identification. This is the “what” pathway. The temporal lobe tells you what you are looking at. Damage to the temporal lobe makes it hard to read, identify faces or watch television.

The temporal lobe is involved in memory of words and personal history. When you can’t find the right word, you are probably having a retrieval problem. It is just a common glitch in the temporal lobe. The temporal lobe also keeps track of what you did last summer.

Auditory information comes from the eyes, passes through the inferior colliculus, then the MGN,  and finally reaches the superior region of the temporal lobe. As it passes through the temporal lobe, sound info is processed with increasing complexity, and shared with the parietal and frontal lobes. The auditory cortex is structured concentrically, with the primary cortex in the middle.

 

Parietal Lobe

The parietal lobe is a multi-fuction region at the top-back of the head. It processes pain, temperature and pressure information. It processes visual information it receives from the occipital lobe (the dorsal stream). And it provides a 3-D view of your environment.

Visual information from the occipital lobe helps you know where things are and how to reach them. Data from occipiatal lobe is compared to data obtained directly from the optic chiasm and superior colliculus. You get fast response to moving objects and a clear, if slower, understanding of where everything is.

Temperature and pain information is routed to the parietal lobe but it is less clear how this information is organized and processed. Touch information is clearly mapped but pain isn’t. Pain also invloves the frontal lobe for determining context and significance.

 

Frontal Lobe

The frontal lobe has three parts: a motor cortex, a pre-motor cortex (including the supplement motor cortex), and the prefrontal cortex.

Motor Cortex

Primary Motor Cortex

Sends signals to the rest of the body to make voluntary movements. A movement is anything we do. So movement and muscles naturally go together. We need muscles to pull on the bones or stretch and shrink. And we need various areas of the brain to plan and execute movements. That’s where having a frontal lobe comes in handy.

Arranged like an upside down homunculus, stimulating the top of the head causes your toes to move. Stimulating the bottom of the motor cortex causes the lips and tongue to move. The motor cortex runs our movements as if we were puppets.

The frontal lobe, basal ganglia, cerebellum and other areas are involved in controlling, planning, regulating and executing movements. What is simple to us as users takes a lot of brain work to accomplish.

Pre-Motor Cortex

Planning of movement occurs in the pre-motor cortex, which includes a region called the supplemental motor cortex. The pre-motor cortex receives input from higher order regions of the brain r=that do long term planning. The pre-motor cortex does the immediate planning and finishing touches, then signals the primary motor cortex to trigger the action.

Prefrontal Cortex

The prefrontal cortex of the frontal lobe is where a lot of thinking goes on. Some regions are better understood than others. The three major sections are dorsolateral, orbitofrontal and ventral-medial. They work together with other regions to make decisions, regulate behavior and anticipate rewards.

This area of the brain is the most likely to get damaged, since it is furthest forward in the head. But it isn’t clear what the actual results will be. You can have a metal rod through your head and have minor difficulties or show no outward damage and have major dysfunction. Damage to the prefrontal cortex typically impairs the ability to learn from rewards and punishments.

Dorsolateral Region

This part of the brain is evolutionarily relatively new. It is the last part of the brain  to myelinate (about age 30). It’s the back part of the frontal lobe; close to the parietal, occipital and temporal lobes. When you experience sleep deprivation, this is the region that gets mad at you. It is involved in executive functions (making decisions), working memory, planning and cognitive flexibility.

This region is connected to the basal ganglia but its big trick is that it makes rules about rules. When you take the Coke-Pepsi challenge unblindfolded, you’ll see the classic shape of the Coke bottle or branding and choose Coke. The dorsolateral region is brand sensitive.

Working memory resides here, or in greatly involved here. Damage to this area is associated with schizophrenia, drug abuse and alcoholism.

 

Ventromedial Region

This part of the brain regulation of emotion, makes evaluations of risk, and involved in decision making. The region in on the bottom of the cerebrum, close to the inside edge of the hemispheres. It grows rapidly during adolescence and young adulthood, allowing much better control of emotions.

Damage to the ventromedial cortex typically results in difficulty choosing between options with uncertain outcomes. It severely impairs personal and social decision making. And there is a large tendency to choose immediate rewards; and be blind to future consequences.

 

Orbitofrontal Region

Anatomically there is no difference between orbitofrontal and ventromedial areas. They differ only in their connections and functions. This area lies just above the eyes (orbits). It is difficult to scan or study because the air-filled sinus cavities are so close. It’s hard to get good images of the area.

Like the dorsolateral cortex, the orbitofrontal cortex is involved in:executive functions, working memory, cognitive flexibility and planning. It seems to be involved in regulating behavior, particularly inhibiting bad behavior.

Damage to this area typically results in emotional outbursts, uncontrolled gambling and drug addiction. This is also the place where Alzheimer’s neural tangles are found.

 

 

 

 

Photo: KT