Brain Structure and Evolution

Topics

• To discuss parceling the brain and in relating brain structure to function.
• To provide a historical context for brain structure-function relationships.
• To illustrate the vertebrate brain plan.
• To provide an overview of the gross anatomy of the nervous system.
• To provide an overview of the vascular system of the brain (online video mini-lecture)

Topic slide

Anatomy seems like it should be a very objective science, but in these topic slides, I illustrate that what one draws can be influenced by one’s preconceptions.

Casseri (1552–1616) was an Italian anatomist who believed that the brain was a vegetative/supportive structure for the ventricles, which he believed to be the loci of brain function. The idea that the ventricles were the seat of cognitive function existed for more than 1000 years. He drew the brain as though it were a coil of intestines.

Vesalius (1514–1564) was a Belgian anatomist who did not subscribe to the ventricular model of brain function. Vesalius drew the brain faithfully to its actual appearance.

Brain Structure and Function

One way to understand a complex system is to break it down into a collection of simpler parts and subsystems. Plato tells us to carve nature at its joints, but where are the joints when it comes to brain structure and brain function?

Consider how would we study the brain if it consisted entirely of a monotonously repeating, homogenous structure. Furthermore, consider that damage, disease, or aging caused a correlated decrement in sensory, motor, emotional, mnemonic, and cognitive processing? Where are the joints upon which to carve in a brain such as that? Such a monolithic structure would present a significant challenge. Indeed, it would suggest that function is represented in a fully distributed manner across a uniform neural architecture.

Happily for us, the brain has recognizably different parts and localized damage and disease causes changes in some processing domains but not others. Thus, there is an implicit belief among many neuroscientists that a different structure implies a different function (this is an intuition, not a law). So, one route to understanding the brain is to understand its major parts, with the belief that this will help us understand its functions.

Major brain divisions are largely preserved in evolution and appear early in development. There is an ancestral vertebrate brain plan, or Bauplan, from which all vertebrate brains including the human brain have evolved (with considerable variation in absolute and relative sizes of components). The variation in the relative sizes of brain components and the appearance of novel components to the Bauplan (such as the appearance of six-layered cortex in mammals, or a layered cerebellum in gnathostomes) allows for cross-species comparative analysis of brain-behavior relationships which can help reveal function.

Box 2.1: Brief Historical Notes

Vital Spirits

Early students of the brain associated function with the fluid-filled ventricles of the brain. Although this may seem silly now, hydraulic principles were well understood in antiquity, but electricity was not yet understood or harnessed.

Galen (129–199 AD) was a Greek-born, Roman physician and anatomist of great stature who wrote over 700 scientific treatises, including On the Usefulness of the Parts. Galen championed a vital spirits theory in which the different ventricles of the brain were responsible for different functions (a structure-function relationship). This theory persisted, in one form or another, for more than 1200 years. If longevity was the measure of a successful theory, the vital spirits theory would be the most successful theory of brain function.

Galen emphasized the rete mirabile, a nexus of arteries and veins that have a net-like appearance, as a key component of his theory. Following Galen, anatomists faithfully included the rete mirabile in their renderings of the human brain for many centuries. However, there is no rete mirabile in the human brain. Due to prevailing anti-vivisection sentiments, Galen didn’t actually dissect the human brain, but rather studied the ox brain. Oxen have a prominent rete mirabile.

Public dissections

Public dissections of humans became part of both scientific and social life in the 1600s. Rembrandt produced two major paintings depicting human dissections. Although a ghoulish spectator event, dissection of the brain led to a better understanding of brain structure. Some structures, when accurately depicted, did not seem to measure up to their exalted position as the seat of intellect. Some attribute the fall of the vital spirits theory of brain function to Da Vinci’s accurate representation of ventricles which he had filled with wax to visualize in 3D. They just didn’t look as impressive in reality as they did in the imagination.

Localization of function

One additional way to carve the brain is to carve along functional joints. When we study the brain’s function (such as movement control, or face processing, or language), we may first attempt to localize functions to different structures or connected systems of structures. We look for dissociations where damage causes the loss of one function but without loss of other functions. For example, damage to one part of the brain may impair the ability to speak but not the ability to understand speech. These patterns of functional-structura ldissociations can help us devise psychological processing models, but can also help us identify brain divisions. We will return to the concept of functional localization in the brain in a subsequent lecture.

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Carving the brain at its joints

Whenever one attempts to understand any complex system as mundane as a car or computer, or as wondrously mysterious as the brain, the first step is usually to break the complex system down into is subsidiary parts and develop a taxonomy or labeling system for those parts.

Before we begin carving the brain at its anatomical joints, let’s recognize that taxonomic systems represent an ordering of nature based upon presumed deep relationships. For example, the taxonomical classification of life forms (e.g., genus and species) represents relatedness of morphology that presumably reflects evolutionary relatedness. All nomenclatures encounter edge cases that don’t quite fit — for example, should the retina be considered part of the brain itself?; are the cranial nerves part of the central or peripheral nervous systems? Is a hagfish a vertebrate? (btw, the consensus is yes, even though the modern hagfish doesn’t have a complete backbone. It presumably degenerated over the course of evolution.)

My own view is that such arguments are often overheated and that the conventions we adopt help us organize our knowledge and communicate with each other in the present. New measures are always being discovered that reinforce or refute the relatedness of different structures and so the taxonomies must be amended. For example, genomic and other molecular data have reorganized many branches of the taxonomic classification of life forms that were previously based on morphology alone, including hominin brain evolution. Gradients of gene expression during development is doing the same for divisions of the neuraxis.

The Vertebrate Brain

I am occasionally conflicted about entitling this course The Human Brain. Yes, most of the content is focused on the human brain. But the title implies that the human brain is discontinuous with the brains of other animals. That is not the case. Much of the genetic and molecular toolkit for making the human brain exists in other species including simple organisms. For example, the most common neurotransmitters in the human brain — glutamate (excitatory) and GABA (inhibitory) — have been found to regulate contraction and relaxation in the sponge, an animal without a brain or nervous system.

It is interesting to note that scientists believe that the sponge is ancestral to the lineage the resulted in humans. The sponge genome contains about 70% of the genes of the human genome.

There is much to learn about brain and behavior from studying neural circuits in invertebrates. Animals such as the worm (C. elegans), the fruit fly (Drosophila), and the sea slug (Aplysia californica) have proved powerful model systems for studying the relationship between genetics, neural circuits, and behavior.

Evo-Devo

As we consider human brain anatomy, we need an organizational structure and a nomenclature. One useful organizational structure reflects both the evolution and development of the brain. When considered together this approach in known as evo-devo.

There are striking commonalties in the brain phenotypes of all organisms who possess brains from insects to humans. For our purposes, we will start with a consideration of the common brain plan observed for vertebrates, from which much of the nomenclature of neuroanatomy is derived.

A lot of what we know about the human brain has come from studies of non-human model vertebrate organisms, such as zebra fish, mice, rats, old-world monkeys, and chimpanzees. Humans are vertebrates, as are fishes, amphibians, reptiles, and birds. Among the vertebrates, humans are mammals like mice and rats. Among the mammals, humans are primates like old-world monkeys and lemurs. Among the primates, humans are great apes like gorillas and chimpanzees. More related species share more commonalities.

To be sure, the capabilities of the human brain far outstrips those of these different species. But many organizational principles apply across these different species with respect to anatomy and function. When novel neural structures or circuits appear — such as the de novo appearance of 6-layered cortex in mammals or the great expansion of orbitofrontal cortex in primates — we can use a comparative approach to attempt to determine their precursors in animals without six-layered cortex or those absent orbitofrontal cortex. In the case of neocortex, for example, it has been argued that the neural circuits represented compactly in 6-layered cortex in mammals are also present in birds who do not have such cortex. But more important for our purposes, we can determine what new capabilities a new or expanded structure or circuit conferred. Thus, comparative psychology and/or comparative neurology can be used to make inferences about brain structure-function relationships across evolution.

However, even as I champion a comparative approach to brain structure and function based upon evolution and development, caution and skepticism are required. In his review of the field of evolutionary and developmental biology, Hall (2012) reminds us that genes have the plans for structure, but that development interacts with the environment (with heat, vibration, chemical signals from other species, and maternal signals about stress). Thus, development is determined by both genetic and epigenetic effects. We will have much to say about epigenetic effects upon brain development later in our discussion of stress and the developing brain. Hall (2012) also cautions us that while development is the earliest and most direct way that evolution can act upon an organism, that evolution can affect all stages of the life cycle.

In Box 2.2 and Box 2.3 below, I consider two evolutionary approaches to development that got it wrong but have nevertheless generated much attention and have influenced other disciplines and popular culture (often for the worse). It is a useful intellectual exercise to understand why each is incorrect.

Box 2.2: Recapitulation Theory

Many of us have heard the phrase “Ontogeny recapitulates phylogeny” which captures the essence of Recapitulation Theory advanced by Ernst Haeckel in 1866. Haeckel famously demonstrated that early stage embryos of various vertebrates (fishes, pigs, salamanders, humans) look remarkably similar. This can be appreciated by examining the top row of the figure below.

Haeckel’s theory stated that during development (ontogeny) an organism went through (recapitulated) all of the stages of prior evolution (phylogeny). So, for example, in the course of development, a human embryo experienced a stage of being a fish. The prominent pharyngeal arches (visible as a row of slits along the ventral head region) adds to that impression by suggesting each species went through a phase of having gill slits. Haeckel’s was once considered a natural law but is wrong. Embryos don’t literally experience stages akin to being a fish or a reptile in the course of developing in a human. Indeed, the pharyngeal arches are derived from the neural crest during development with each segment serving as the progenitor tissue for the bones, muscles, glands, connective tissue, and nerves of the face and neck. Despite their appearance, they are not gills and human embryos did not transition through a ‘fish phase’.

So, if Haeckel’s theory is wrong, and we don’t literally recapitulate the evolutionary history of our species during our development, why do these early stage embryos look so similar? And what is the relevance of this discredited theory to a course on the human brain anyway?

There are useful insights from Haeckel’s observations that are concisely summarized on this webpage at McGill University. The main point is that closely related species, such as the vertebrates illustrated in Haeckel’s illustration, have a common body plan that is conserved across evolution. As we will see below, that extends to a common brain plan, or Bauplan. Because the success of later stages of development are dependent upon getting the early stages right, mutations that affect early embryonic growth are usually lethal. Thus, divergences among species tend to occur later in development. Thus, the similarities among early stage embryos represent commonalties among vertebrates that then futher develop into adult forms.

Darwin’s theory of evolution was a biological theory, but which was later applied by others to social behavior and economics (‘survival of the fittest’) to justify social and economic inequality and racism. Recapitulation Theory was later applied to social development and similarly used to justify nationalistic and racist policies.

Box 2.3: The Triune Brain

One provocative hypothesis purportedly based on evolution that continues to capture public attention is the Triune Brain hypothesis by Paul MacLean (Yale School of Medicine ’40) (The triune brain in evolution: role in paleocerebral functions. New York: Plenum Press, 1990). Whenever you hear people refer to their ‘reptilian brain’; they are making an allusion to MacLean’s theory. MacLean proposed that the brain is made up of three layered structures: a reptilian brain responsible for basic house-keeping functions, a mammalian brain responsible for emotions and memory (e.g., MacLean introduced the term ‘limbic system’ to refer to this mammalian brain), and a primate/human neomammalian brain (mostly consisting of neocortex) responsible for cognition, intellect, and spiritual values.

• Layer 1 (reptilian brain, ‘R’ complex)
• Layer 2 (mammalian brain, ‘limbic system’)
• Layer 3 (neomammalian brain)

Here is a representation of the Triune Brain with anatomical structures on the right and functions on the left.

This three-layered, or Triune Brain hypothesis, suggests that reptiles did not have Layers 2 and 3. This is wrong. The hypothesis also implies that the lower layers did not further evolve but were rather ‘layered over’ during evolution by limbic and neocortex. This is also wrong. Yes, the huge expansion of neocortex over the course of evolution is obvious — but there was also coordinated growth in the size and complexity of subcortical structures.

Nevertheless, this hypothesis does capture the notion that higher level brain structures strongly influence lower-level brain structures and can inhibit automatic responses to stimuli. For example, our hypothalamus (part of MacLean’s limbic brain) can receive signals from bodily sensors indicating that we require food and it can initiate behaviors to acquire food. However, we can watch advertisements for tasty food items that require the engagement of higher cortical regions (MacLean’s neomammalian brain) and also initiate behaviors to acquire food, even though we may not need food at that time. Conversely, we can be sensitive to those hypothalamic signals and experience hunger, but override food seeking behavior due to a higher-order plan to diet.

We will discuss levels of control later in the semester. We will also discuss the concept of disinhibition — e.g., damage to a brain structure that appears to ‘inhibit the inhibition’ that a higher brain area was exerting on a lower-level function.

There is an interesting parallel noted by some between the Triune Brain hypothesis and Freud’s psychodynamic theories of the Id, Ego, and Superego.

Vertebrate brain Bauplan

The following figure from Sugahara (2017) illustrates the inferred brain plan for the last common ancestor (LCA) of all vertebrates which lived about 500 mya.

There is much to this figure, which will be discussed in more detail below. For now my point is to just to emphasize that vertebrate brains develop from a plan that is recognizably similar across the 54,000 vertebrate species, from the lamprey to the human.

But wait, didn’t we just spend a lecture on the differences among brains in terms of absolute and relative size? How do vertebrate brains end up differing in size and how do different brain regions differ in size relative to the rest of whole brain. There are many reasons, but the concept of heterochrony is important in this regard. Heterochrony is concerned with the duration and timing of developmental events which control the rate of development. The timing and duration of genetically regulated processes can result in more or less of some gene products which results in larger or smaller phenotypes (such as brain structures). Indeed, when examining vertebrate brains across widely divergent species, one can appreciate the relative size differences of different brain structures. This can be seen in the following figure from Kawakami and Murakammi (2017) compares brains of different vertebrates. Note the commonalities among brain structures and overall brain plan but the differences in relative sizes of those structures.

But what is the substrate on which heterochrony works? How can some brain areas expand while others do not? The answer comes from a more thorough understanding of how an embryonic brain differentiates into different brain structures. As discussed in more detail below, different regulatory genes control the development of different parts of the Bauplan illustrated above. These regulatory genes are, of course, subject to the pressures that drive evolution.

Brain development

For me, human brain development is intrinsically interesting and the relationship of development and evolution is fascinating. However, even if you don’t share my fascination, it is an important area of study in that irregularities in development — both subtle and severe — are associated with disorders such as schizophrenia, bipolar disease, ASD, and a host of other neurodevelopmental disorders. Preventing and treating these disorders will depend upon understanding the neurogenetic sequences that underlie development. This is an enormous topic in its own right, so I will highlight just a few processes below to give you a sense of the field.

Gastrulation and neurulation

Shortly after fertilization (about five days in humans), a hollow ball of cells forms which is known as the blastula. The blastula undergoes a differentiating process known as gastrulation which is summarized below. Gastrulation occurs during the third week post-conception in the human embryo.

“Gastrulation is defined as an early developmental process in which an embryo transforms from a one-dimensional layer of epithelial cells (blastula) and reorganizes into a multilayered and multidimensional structure called the gastrula. In reptiles, avians, and mammals, which are triploblastic organisms, gastrulation derives a three tissue-layered organism composed of endoderm, mesoderm, and ectoderm; each germ layer corresponds to the development of specific primitive systems during organogenesis.”

The nervous system develops from the outer of the three germ layers, the ectoderm. During a process called neurulation, this outer layer develops a groove which eventually closes over and becomes the neural tube. Cells line the interior of the neural tube and it is from these cells that the structures of the brain and spinal cord develop. The cells in different regions of the neural tube are patterned by different regulatory genes into specialized brain regions. That is, different areas of the neural tube are under the control of different regulatory genes. This is the substrate on which heterochrony can act to change the sequence and duration of development of different brain regions. I will describe this substrate in more detail in the next section.

Divisions of the neural tube

The patterning occurs in a grid-like manner along two major axes. Imagine a tube layed out on a table with one side against the table (the bottom, belly, or ‘ventral’ side) and one side upwards (the top, back, or ‘dorsal’ side). The top half is the alar plate and the bottom half is the basal plate. This dorsal-ventral axis forms one dimension of cellular differentiation. Now imagine that the tube is also segmented (think ‘worm’) along its longitudinal (its anterior-posterior, or A-P, or rostral (beak)-caudal (tail)) axis. These segments are called neuromeres.

To help visual this initial patterning, I made a mashup of figures from Rubenstein and colleagues (1994) on the left and from the Wikepedia on the right. Both of these images represent the vertebrate Bauplan but drawn to emphasize different organizational principles (note that the images are reflected from each other, so that the ‘head’ is on the right for the leftmost figure, and the ‘head’ is on the left for the rightmost figure). Note that in both images, there is a kink or bend in the anterior part of the neural tube near the head.

The right image shows the division between the alar and basal plates described above, and illustrates how that division extends along the length of the neural tube. This differentiation has functional meaning. For example, the alar (dorsal) plate in the spinal cord develops into a sensory input region while the basal (ventral) plate develops into a motor output region. We will discuss this organization in detail in the lectures on sensory systems.

The left image shows the the segmentations or neuromeres. The neuromeres are numbered. R1 through R8 represent rhombomeres, the single M is a mesomere, and the P1 through P6 are prosomeres. Note that the some researchers divide neuromeres into two and so there are descriptions of 12 rhombomeres in some more modern formulations and 2 mesomeres.

Prosomeric model

Neuromeres are controlled by the action of different genes and thus provide a substrate on which evolution can affect to the functional organization of the brain. Puelles and Rubenstein (1993) put forth the prosomeric model of neural development to describe this segmental numerometric model. In the hindbrain, or rhombencephalon, these appear as a sequence of eight swellings referred to as rhombomeres.

Summarizing from here and additional sources:

• Rhombomeres are self-governing developmental units. Each rhombomere expresses its own combination of transcription factors. Thus, each rhombomeres has distinct molecular cues and its own pattern of neuronal differentiation.
• Every rhombomere develops its own set of ganglia and nerves, which are related to the formation of cranial nerves.
• Different rhombomeres are associated with central pattern generators such as those associated with respiration, chewing, and walking.

More recently, it has been recognized that the prosencephalon (forebrain) is also organized into segments called prosomeres. These are less obvious to visual inspection than rhombomeres and are primarily evident by staining for molecular markers that represent the circumscribed expression of specific genes. Thus, prosomeres represent a neural segmentation defined by regulatory genes that arose through evolution. This raises the intriguing idea that prosomeres represent the development of functional brain units.

Bumps along the neural tube

Neuromeres contribute to morphometric changes along the long axis of the neural tube that are evident a protuberance, or bumps, in its shape.

The neural tube first develops three major protuberances:

• Forebrain or Prosencephalon (organized by prosomeres)
• Midbrain or Mesencephalon (organized by mesomeres)
• Hindbrain or Rhombencephalon (organized by rhombomeres)

These major protuberances are visible in the human embryo at day 25. By day 30 in the human embryo, the Forebrain and Hindbrain each differentiate into two additional protuberances, leaving a total of five distinct brain regions:

1. Myelencephalon – medulla (derived from Rhombencephalon)
2. Metencephalon – the pons and cerebellum (derived from Rhobencephalon)
3. Mesencephalon or midbrain – the tectum (superior and inferior colliculi) and tegmentum
4. Diencephalon – the thalamus, hypothalamus, epithalamus (derived from Prosencephalon or Forebrain)
5. Telencephalon, cerebral cortex plus hippocampus, amygdala, and basal ganglia (derived from Prosencephalon or Forebrain)

Occasionally, the neural tube fails to close during development leading to spina bifida (posterior end of tube doesn’t close) or anencephaly (anterior end of tube doesn’t close). Recently, there have been many reports of anencephaly or microencephaly associated with the Zika virus. The Zika virus attacks the neural tube during development.

I will make continuing reference to these brain divisions as we discuss the major structures that are derived from these protuberances.

Box 2.4 Development of the Telencephalon

The telencephalon is the location of multi-modal sensory and motor integration and the site of higher cognition in humans and other animals. The telencephalon is part of the vertebrate brain plan, but it is the part of the plan that is most variable across vertebrate species. All mammals have six-layered neocortex, and differences among mammals are largely related to the number and extent of particular neocortical regions. Much of the evolutionary variability in the telencephalon is found among non-mammal vertebrates. Reptiles, for example, have three-layered cortex while avians (birds) do not have a laminated cortex but rather have specialized nuclear groups such as the Wulst. Homologies between mammalian neocortex and the telencephalon in non-mammals have been controversial. Karten (2015), for example, has argued that the avian (bird) brain has much of the circuitry of mammalian neocortex, but that the circuit is more distributed among nuclear groups in the avian brain. Briscoe and Ragsdale (2019) present a good summary of the evolution of telencephalon in vertebrates for those interested in pursuing this topic.

The telencephalon experiences developmental stages as discussed above on evo-devo. During development, the telencephalon can be divided into a dorsal pallium and a ventral subpallium during development. In a rough accounting, the dorsal pallium gives rise to cerebral cortex, the hippocampus, the basolateral nuclei of the amygdala, and most excitatory neurons. The subpallium gives rise to the basal ganglia (or striatum), the preoptic area of the hypothalamus, the corticomedial nuclei of the amygdala, and most inhibitory neurons.

Adding more detail, the subpallium is divided into four regions: the medial ganglionic eminence (MGE), the lateral ganglionic eminence (LGE), the preoptic area, and the septum.

It is notable that the MGE is the birthplace of most of the GABA-ergic inhibitory interneurons that migrate and eventually populate neocortex. Dysfunction in inhibitory interneurons have been implicated in a number of neuropathologies such as epilepsy, schizophrenia, and autism. Transplantation of interneuron stem cells, such as those that populate the MGE and other subpallial regions, is being explored in non-human animal preparations as possible therapies for such disorders.

The pallium can be divided into different regions that can be identified by molecular markers that reflect the expression of regulatory genes that pattern cortex. The number of such regions demarcated regions of the pallium has increased with as new molecular markers are tested, and is likely different for different species. Recent studies of the human brain suggest that six such regions may exist. One such region of the pallium, the medial pallium, develops into an anatomically recognizable hippcampus in mammals. Molecular markers that demarcate the medial pallium in other vertebrates have been used to identify brain regions in non-mammalian vertebrate species (such as birds, for example) that don’t have the same morphology as a mammalian hippocampus, but which appear to support a subset of similar functions. These evo-devo homologies thus provide powerful comparative evidence for brain structure-function relationships.

It is notable that the amygdala, a collection of 13 nuclei in the anterior temporal lobe of humans that has been related to processing emotion, motivation, and salience, is both pallial and subpallial in origin. The corticomedial nuclei which are associated with olfaction are subpallial in origin, while the basolateral nuclei which have been associated with fear conditioning are pallial in origin. This is evidence against the simplistic notion of evolution represented in the Triune Brain hypothesis discussed above, as it demonstrates that a so-called ‘reptilian’ structure such as the amygdala is under continuing evolution and expansion under control of the pallial regions of the developing telencephalon. As the pallium evolves and controls the expansion of neocortical areas, it also controls the expansion of newer nuclear components of the subcortical amygdala.

Among mammals, there are many commonalities among pallial derived cortex — particularly with respect to primary sensory cortices. The figure below from Briscoe and Ragsdale illustrates the ancestral mammalian cortex on the left (note that much of cortex is devoted to olfaction) and the cortical distribution and size of primary sensory cortices for vision, somatosensation, audition, and other regions. This is illustrative of the conservative nature of telencephalic evolution in mammals.

We will spend the majority of the semester discussing the functions of the telencephalon, its cortical regions and its large subcortical regions the basal ganglia, amygdala, and hippocampus.

The Peripheral Nervous System (PNS)

Although the focus of this course is the brain itself, the brain communicates with the entire body — controlling muscles, receiving sensory information, stimulating the release of releasing factors and hormones that communicate with other glands, and managing routine functions like breathing and thermoregulation. A more encompassing term for all of this is nervous system.

There are two major divisions of the nervous system: the peripheral nervous system (PNS) and the central nervous system (CNS). We will discuss each briefly below, along with their subdivisions.

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The PNS refers to components of the nervous system that are outside of the brain and spinal cord. There are two major components of the PNS, the Autonomic Nervous System (ANS) and the Somatic Nervous System (SNS).

Autonomic nervous system (ANS)

The autonomic nervous system refers to nerves that innervate bodily organs, such as the heart, lungs, and the mucosa of the alimentary canal. There are three components of the ANS, two of which (sympathetic and parasympathetic) innervate the same organs but generally have opposing effects. If one conceives of the sympathetic nervous system as the ‘accelerator’, then the parasympathetic can be thought of as the ‘brake’. The ANS plays an important role in our response to stressors, and is affected by emotional states like fear, and the release of hormones like adrenalin and cortisol. We will discuss these topics later in the semester and, for that reason, I will describe the ANS briefly now.

Enteric Nervous System

The Enteric Nervous System contains about 400–600 million neurons that monitor and coordinate activity in the alimentary canal (gut or GI tract). About 90% of serotonin and 50% of all dopamine is used in the enteric nervous system. Although the enteric nervous system can operate independently from the brain, it does communicate with the brain. There is some evidence of brain involvement in diseases of the gut, such as irritable bowel syndrome. There are also tantalizing suggestions that some diseases that affect the brain may begin by viral or other infections of the gut that are communicated to the brain through cranial nerves such as the vagus nerve. These include some forms of Parkinson’s disease, ALS, and autism.

There is also a fast growing body of evidence that the microbiota of our gut can directly influence brain activity; particularly in response to stress and anxiety. Other evidence suggests that the brain can influence the gut microbiota, suggesting that communication is bidirectional.

Sympathetic Nervous System

The Sympathetic Nervous System is responsible for our Fight or Flight response to stressors. The sympathetic nervous system speeds heart rate and respiration, and inhibits digestive functions (among other functions shown in the image below).

Parasympathetic Nervous System

The Parasympathetic Nervous System is our Rest and Digest or Feed and Breed system. The parasympathetic nervous system slows heart rate and respiration, and facilitates digestive functions (among other functions shown in the image below).

The generally opposing nature of the sympathetic and parasympathetic nervous systems are illustrated below. Note, however, that activation of both systems is necessary for some coordinated activity — for example, sexual behavior.

Psychophysiological methods can measure ANS activity

Psychophysiological methods measure the interplay between sympathetic and parasympathetic activation of certain bodily organs. We are familiar with some of these measures from the realm of lie detection that use a polygraph (a polygraph is essentially a time chart of several physiological responses obtained during stressful questioning). The general idea in psychophysiological measurement is that stress/arousal is reflected by increases in sympathetic nervous activity. Here are some common psychophysiological measures used in psychology laboratories:

• Pupillometry: The pupils contract and expand as a function of mental load, attention, and stress.
• Skin conductance response: The sweat glands (eccrine glands) increase activity during stress, and this can be measured as a change in the conductance of skin to weak electrical current. Sweaty skin has lower electrical resistance. The SCR is sometimes referred to as the galvanic skin response (GSR) or electrodermal response.
• Heart rate and heart rate variability: Heart rate increases and heart rate variability decreases during stress. This relationship reverses during relaxation.
• Respiration – breathing rates increase during stress.

Somatic Nervous System (SNS)

The Somatic Nervous System encompasses the nerves that exit and enter the spinal cord. Some of these nerves are sensory, some are motor, and some are a mix of sensory and motor fibers.

We will discuss the anatomy of the somatic nervous system in detail later in the semester. Let me note here for the sake of completeness that the motor nerves have their cell bodies in the ventral horn of the spinal cord. The axons from these motor neurons leave through the ventral roots of the spinal cord and innervate the appropriate muscles.

The sensory nerves have their cell bodies in the dorsal root ganglia, a collection of neuronal cell bodies that lies just outside of the spinal cord. The axons from the sensory neurons enter the dorsal horn of the spinal cord through the dorsal roots.

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Central Nervous System

We will have much more to say about the CNS below, which consists of the brain and spinal cord; i.e., the part of the nervous system that is covered in bone. Many of the topics introduced briefly below will be elaborated in later lectures.

Orientation around the neuraxis

Just as we use the terms higher or lower to describe the relative positions of things in the world, we need agreed upon terms to describe the relative locations of brain parts.

Cardinal viewing planes

There are three cardinal axes for describing views of the body, or, in our case, the CNS and brain. Imagine that we have made a cut exposing a plane of the brain.

• Axial or horizontal or transverse (as though we are looking down from above).
• Sagittal (as though we are looking from the side).
• Coronal or frontal (in radiological convention, it would be as if you were looking at the brain from the front, thus the left side of the brain is on the right side of the image).

Relative anatomical terms

Throughout the course, I will often describe a brain structure’s location using relative terms to another structure’s location. There are english and latin terms for these relative locations.

• Anterior or rostral (rostrum means beak in Latin)
• Posterior or caudal (cauda means tail in Latin)
• Dorsal or superior in the brain proper, in the spinal cord, dorsal is located towards the back (think dorsal fin on a shark)
• Ventral or inferior in the brain, belly side of the spinal cord (from the latin ventralis, which means belly)
• Medial means toward the middle
• Lateral means towards the edge

In addition, there are modifiers.

• Pre usually means ‘anterior to’, so pre-optic means just anterior to the optic area, and prefrontal means the anterior part of the frontal lobe.
• Post usually modifies a structure that is posterior to another better known structure. So, the post-central gyrus is the first gyrus posterior to the central sulcus.
• Extra usually means ‘around but outside of’, so extrastriate cortex means the cortex that is not striate, but just around and abutting striate cortex. It does not mean ‘additional’.
• Reticulum or Rete refer to structures that have a net like appearance.
• Hypo usually refers to a brain structure that is below another brain structure. For example, the hypothalamus sits below or ventral to the thalamus.
• Neo means new, and it usually refers to a structure that has been later in evolution than the reference structure. For example, neocortex is an evolutionary more recent type of cortex than the more primitive allocortex. The neocerebellum is a more recent development of the cerebellum from an evolutionary perspective than the more ancient vestibulocerebellum.

So ventromedial prefrontal cortex means the inferior part of anterior frontal cortex towards the middle of the brain.

Meninges and Cerebrospinal Fluid (CSF)

The brain is encased in three layers of coverings, or meninges, within the skull:

1. Dura mater (tough mother) is a thick ‘baggie’ that is the outermost covering.
2. Arachnoid (spider) is a web-like intermediate layer
3. Pia mater (tender mother) is the thin innermost layer that appears ‘shrink-wrapped’ to the brain’s surface.

The figure above was copied from www.earthslab.com and can be found here.

Cerebrospinal fluid (CSF) is generated in the ventricles by tissue called the choroid plexus. The CSF bathes the brain between the dura and arachnoid layers of the meninges. The CSF has three useful properties:

• The first is buoyancy for the brain. A brain in fluid weighs less than a brain on a table top. The brain cannot support its own weight, and would compress blood vessels.
• The second is that it helps protect the brain from injury as it acts as a shock absorber.
• The third is that it removes waste. One example of this is the spinal tap or lumbar puncture through which CSF is extracted an analyzed for evidence of infectious agents.

The CSF circulates around the brain and spinal cord. If its circulation is blocked, it can lead to the clinical finding of hydrocephalous. Nowadays, hydrocephalus is usually detected early, and a shunt is placed into the brain to drain the excess CSF.

Cranial nerves

There are twelve large cranial nerves that have their sources in the brain. Some of these nerves exit the brain through holes in the skull. I color-coded the source within the brain of each cranial nerve.

• Cranial Nerves 1 and 2 originate in the forebrain.
• Cranial Nerves 3 and 4 originate in the midbrain (mesencephalon)
• Cranial Nerves 5–8 originate in the pons (metencephalon)
• Cranial Nerves 9–12 originate in the medulla (myelcenphalon)

The twelve nerves, and their general functions, are as follows:

1. Olfactory – smell
2. Optic – vision
3. Oculomotor – control of eye muscles
4. Trochlear – control of eye muscles
5. Trigeminal – sensation in face, biting, chewing
6. Abducens – control of eye muscles
7. Facial – facial expression, anterior taste
8. Vestibulocochlear – balance and hearing
9. Glossopharyngeal – tongue and pharynx, posterior taste
10. Vagus – control of heart among many other functions
11. Spinal accessory – control of neck muscles
12. Hypoglossal – muscles of the tongue

If you have aspirations to become a neurologist, you will learn the route and function of these nerves in great detail. One popular mnemonic for remembering the twelve nerves is the following phrase: “On old Olympus’s towering top a Finn and German viewed some hops”. The first letter of each word in the phrase is the first letter of each of the nerves in order.

There are many clinical syndromes associated with cranial nerve damage, and these can be indicators of other problems, such as compression of the cranial nerve by a tumor. Here are some examples:

• Facial nerve and Bell’s palsy
• Trigeminal nerve and trigeminal neuralgia
• Optic nerve and optic neuritis
• Vestibular nerve and labyrinthitis

Brain structures arising from the differentiation of the neural tube

Here we pick up the discussion of major brain divisions that are common to the vertebrate brain, and focus on the human brain. I have adapted a figure from the Wikipedia below that presents a stylized version of the major brain divisions discussed earlier. On the left of the figure are the three intial protuberances: Prosencephalon, Mesencephalon, and Rombencephalon. On the right we see that the Prosencephalon is divided into Telencephalon and Diencephalon, and the Rhombencephalon is divided into Myelencephalon and Metencephalon. I had added major structures that develop from these regions in red font on the right of the figure.

The figure below is a concept map illustrating these divisions in a different format.

Myelencephalon

The Myelencephalon and Metencephalon form the Rhombencephalon or hindbrain.

Medulla oblongata

The medulla oblongata derives from the myelencephalon, and is the brain component that sits atop the spinal cord as it enters the skull case from below. The medulla includes a collection of small nuclei that play a critical role in essential bodily functions that control breathing and heart rate, vomiting, and other functions. The nuclei of origin for four cranial nerves are located within the medulla, and many white matter fiber tracts course through the medulla as they pass between the spinal cord and brain.

Metencephalon

The Metencephalon and the Myelencephalonform the Rhombencephalon or hindbrain. It is composed of two main areas: the cerebellum and the pons.

Cerebellum

The cerebellum (‘little brain’) along with the Pons form the Metencephalon. The cerebellum is a remarkable structure that sits ventral to the telencephalon and caudal to the midbrain. The cerebellum is related to motor control, motor planning. posture, and balance.

Pons

Pons means ‘bridge’ in Latin. The pons is a complex region containing the nuclei for four cranial nerves, the Olivary complex which communicates with the cerebellum, the inferior olive which is concerned with hearing, and numerous other nuclei concerned with essential bodily functions such as sleep. Many white matter fiber tracts course through the pons.

Mesencephalon (midbrain) or tectum

The term tectum refers to two pairs (one per hemisphere) of nuclei, the colliculi). The superior colliculus (aka, optic tectum) plays an important role in vision and multi-modal spatial registration important for directing eye movements. The inferior colliculus plays an important role in audition.

Diencephalon

The diencephalon and telencephalon were both derived from the forebrain or prosencephalon. The diencephalon is composed of the thalamus, hypothalamus, and epithalamus. We will consider the thalamus and hypothalamus below.

Thalamus

The thalamus is a collection of 13 bilateral pairs of nuclei (some of which are further subdivided) that are situated in the middle of the forebrain. Many of the thalamic nuclei are deeply related to specific sensory systems. For example, the lateral geniculate nucleus of the thalamus receives input from the optic nerve from the eyes and projects visual information to primary visual cortex in the occipital lobe. Other thalamic nuclei play a similar role in audition and somatothesis. Still other thalamic nuclei connect different areas of neocortex, and cortical regions to the cerebellum and basal ganglia.

Hypothalamus

The hypothalamus is a collection of 16 small nuclei that are involved in many brain and bodily functions such as thermoregulation, sexual arousal, hunger and satiety, and sleep cycles (homeostasis). There are secretory cells in some hypothalamic nuclei that are involved in neuroendocrine (brain-hormone) function.

As an example of this brain-endocrine function, we will learn during my lectures on stress that that the paraventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing hormone (CRH) which act on the pituitary gland to release another hormone (ACTH) which then is released into the blood stream . ACTH stimulates the adrenal glans to release adrenaline and glucocorticoids, hormones involved in stress and the ‘fight or flight’ response. Thus, the hypothalamus is a key area of the brain involved in our response to stressor.

Epithalamus

The epithalamus contains the pineal gland (which unlike most brain structures, does not exist as a left-right bilateral pair). The pineal gland secretes melatonin and regulates circadian rhythms.

Telencephalon

One of the visually striking aspects of the telencephalon is that is has two distinct halves, or hemispheres joined together at the midline. Although the hemispheres look similar to the naked eye, we will learn that they have remarkable different capabilities when we study ‘split-brain’ patients later in the semester. For example, the left hemisphere is critical important for language, as we will see in our lectures on language and the brain.

Neurons and cortex

The principal cells of the brain are neurons and glia. We will discuss neurons and glia in detail in our next lecture. However, for our present purposes, understand that neurons are the primary cells for information processing, in that they receive input from other neurons and send output to other neurons. This communication occurs over thin tubular protoplasmic processes called axons, that can travel from the neuron’s cell body to quite distant regions of the brain.

Neurons can be arranged in clusters, or nuclei, within many regions of the neuraxis. However, in the telencephalon (or forebrain) of humans, neurons are principally organized in a thin continuous sheet 2–4 mm thick and 1.3 square feet in area (per hemisphere). We call this continuous sheet cortex (Latin for ‘bark’) that wraps its surface. The neurons are organized into layers within cortex, and the layers are segregated by their different kinds of connections (e.g., input layers and output layers) and different kinds of neurons.

There are two principal forms of layered cortex:

1. Allocortex
   There are two forms of allocortex, both of which are found primarily in the the rim of cortex that forms the limbic system.
   • Archicortex
     • Archicortex has 3 layers and is thought to be an ancient form of cortex. In humans, it is found in the hippocampus and olfactory cortex.
   • Paleocortex
     • Paleocortex has 3 or 4 layers and is found in several regions of the human brain, principally in the parahippocampal gyrus and perirhinal cortices, and in parts of cingulate cortex.
2. Neocortex.
   • Neocortex contains 6 layers and is only found in mammals. In humans, most of the vast cerebral cortex is 6-layered neocortex.

Divisions of cortex

Here is a narrated video overview of cerebral cortex (~17 minutes). You may need to enable third party cookies to view this video.

Errata: In the video, when pointing to the auditory nerve, I misspoke and called it the 7th cranial nerve. It is, of course, the 8th cranial nerve. Also, at about the 15 minute mark, I misspoke when I referred to a transition between temporal lobe and occipital as being between the parietal lobe and occipital lobe. At some point I will edit this video to fix these errors, but for now be aware.

Gyri and Sulci

The continuous sheet of cortex that wraps the telencephalon or forebrain is folded so that more surface area can be fit inside the bony skull. The part of cortex that is exposed on the surface is called the gyrus (plural, gyri) and the part of the continuous sheet of cortex that is folded inward between the gyri is called the sulcus (plural, sulci). Although there is variability across individuals, the major sulci and gyri have a very similar layout, are recognizable across individuals, and have names (such as the central sulcus, the fusiform gyrus). This suggests that folding patterns are not random, but may be optimized for connections among neurons.

Lobes

It is customary to divide up the gyri and sulci of the continuous sheet of cerebral cortex into larger units called lobes. There are four major lobes:

• Frontal
• Temporal
• Parietal
• Occipital

In addition, many refer to the insula, a portion of cortex hidden by the convexities of the frontal and temporal lobe, as a lobe. Historically, the cingulate gyrus and adjacent cortex on the midline of the brain have been referred to as the limbic lobe.

Deep telencephalic structures

In addition to neocortex, the forebrain contains three large deep structures that we will consider in detail later in the semester. These include:

• amygdala (a collection of 13 nuclei related to emotion, fear, and motivated behaviors)
• hippocampus (a structure related to spatial navigation and memory and a target of stress)
• basal ganglia (a complex structure consisting of several nuclei that is related to the selection and inhibition of movements and behaviors related to the reward system).

Brain facts

The human brain has ~86 b neurons. The cerebral cortex is ~82% of brain mass but contains only 19% of its neurons. The cerebellum is 10% of brain mass but contains 81% of neurons.

You can find many interesting quantitative facts about the human brain and the brains of other species at this Washington University website.