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Neuroanatomy in Physical Therapy
by Annie Burke-Doe, PT, MPT, PhD
Associate Professor, University of St. Augustine for Health Sciences at San Diego

Slide 1: Neuroanatomy in Physical Therapy

Welcome to Neuroanatomy in Physical Therapy. I am Dr. Annie Burke-Doe, a practicing physical therapist and an associate professor at the University of St. Augustine for Health Sciences in San Diego, California.

This lecture series has been developed for physical therapists embarking on the study of neurology. Neuroanatomy is the study of the anatomical organization of the brain and it is also considered a branch of neuroscience, which deals with the study of the gross structures of the brain and the nervous system.

One of the elements of neuroscience that makes it such an interesting topic is that it will draw from knowledge of many disciplines including anatomy, physiology, biology, and pathology. Neuroscience helps us appreciate how the nervous system works together, both as a whole to perform such acts as thinking, perceiving, movement, and communication.

In clinical practice, it is important to understand how the nervous system develops, how specific regions function and communicate with each other, how these connections give rise to our motor acts, and how experience or pathology can alter these functions. This knowledge will allow us to provide appropriate care for our clients with nervous system dysfunction. We will begin the lecture series with the overall organization of the nervous system.

Slide 2: Anatomical Divisions of the Nervous System

Once we have oriented ourselves to the basic anatomical and main components of the nervous system as a whole in this slide series, we will then proceed to a more detailed explanation of each component of the nervous system.

As you can see here, the nervous system can be subdivided into the central nervous system, or CNS, and the peripheral nervous system, or PNS. The CNS consists of the spinal cord and the brain. The PNS includes all neural tissue outside of the CNS, which consists of cranial nerves, which control sensory and motor functions to our head and neck; the spinal nerves, which control motor and sensory function in our trunk and extremities; the sympathetic and parasympathetic, which control autonomic functions of the body; and the enteric nervous system, which controls the functions of the gastrointestinal system.

Slide 3: The Central Nervous System and Peripheral Nervous System

The spinal cord and brain, here depicted in light blue, are complex organs that include neural tissue, blood vessels and connective tissue. The connective tissue is the framework or scaffold to support and protect the CNS. The CNS is responsible for integration, processing and coordination of incoming sensory information; we call that in the afferent direction. You are touched out in the periphery and the information comes into the body afferently. When integrating outgoing motor commands, or effects, we call that the efferent direction. The CNS is also responsible for higher level functions such as learning and memory.

The PNS, depicted here in black, includes all of the neural tissue outside of the CNS, such as the spinal and cranial nerves. The PNS delivers that sensory information afferently to the CNS and carries out motor commands efferently to the peripheral tissues and systems.

I want you to remember that this material presented may take some time to integrate and that you will gradually, as we progress through additional slides and lectures, potentially have to come back to this material to reinforce the learning.

Slide 4: Embryological Development

In order to understand the internal organization of the adult brain, we must consider its embryological origins, or the early growth and development of the fetus. During embryological development, the CNS begins from a germinal layer of ectoderm cells that fold over to form a hollow cylindrical tube, known as the neural tube. This tube has a fluid filled internal cavity, known as the neurocele. Cells from within and at the crest of the neural tube will become the PNS. The cephalic, or head section of the neural tube, will develop three distinct brain expansions, called primary vesicles, which expand rapidly and eventually develop into the brain, while part of the neural tube, running down the back of the embryo, forms the spinal cord. The fluid-filled cavities within that neural tube will develop into the ventricles, which form and contain CSF that will bathe the brain and the spinal cord. The primary vesicles, pictured here in a lateral view of the embryo, are named for their relative positions:
  1. The prosencephalon, or forebrain, in green
  2. The mesencephalon, or midbrain, in red
  3. The rhombencephalon, or hindbrain, in orange
Slide 5: Development (Cont.)

Let's look at the fate of those three primary vesicles during development. The forebrain, or prosencephalon, is considered the largest part of the nervous system in humans and, over time, will further subdivide into the telencephalon and the diencephalon. The telencephalon comes from the Greek "telos," meaning "end," and encephalon meaning "brain." It will be made up of cerebral hemispheres, and includes structures discussed later such as the cerebral cortex, white matter, and the basal ganglia. The diencephalon is composed of the thalamus, hypothalamus, and associated structures. Our midbrain, or mesencephalon, produces a small mass of neural tissue with an aqueduct of the midbrain, which will form a connection between the third ventricle and the fourth ventricle. It is relatively a short, narrow region connecting the forebrain and the hindbrain. The rhombencephalon, the hindbrain, is composed of the pons and the dorsal portion of the metencephalon, which will become the cerebellum together with the medulla or the myelencephalon. The midbrain, pons, and medulla together form a connection between the forebrain and the spinal cord. Since the forebrain sits on the top of the midbrain, pons, and medulla, almost like cauliflower on its stalk, these structures are often referred to as the brainstem. The brainstem is the most ancient part of the human brain and is the part that most closely resembles the brains of fish and reptiles. It controls many of our most basic body functions necessary for survival. It has a respiratory area and a control of blood pressure and heart rate as well.

Slide 6: Cerebrospinal Fluid

Cerebrospinal fluid (CSF) is formed mainly by vascular tufts lying within the ventricle called choroid plexus. The CSF will circulate from the choroid plexus, to the lateral ventricles, to the third ventricle, and then leave the ventricular system via the foramina in the fourth ventricle, which then allows it to percolate around the outside surface of the brain and the spinal cord. It provides cushion and support for the brain and nervous system, and it has the ability to transport nutrients, chemical messengers, and wastes.

Slide 7: Cranial Meninges

The nervous system is covered by three membranous protective layers called meninges. The layers that make up these cranial meningis are called the cranial dura mater, the arachnoid mater, and the pia mater. These coverings are continuous with the spinal cord coverings, or spinal cord meninges. Their basic role is to support the brain inside the cranial vault, like a seat belt of a car, as the brain floats in the CSF. These cranial meninges, additionally in several locations, will extend into the intercranial cavity forming a sheet that will dip downward, into the brain, and then return. These are called dural folds. The dural folds provide additional stabilization and support for the brain, and the three largest are:
  1. The falx cerebri, which is the dural fold that projects between the cerebral hemispheres in the longitudinal fissure, or the right and left half of the brain
  2. The tentorium cerebelli is the second dural fold that is going to protect the cerebellar hemispheres, which are in the back of your brain, and separate them from the cerebrum
  3. And finally, the falx cerebelli, which is going to divide the two cerebellar hemispheres and protect and support
Slide 8: Six Major Brain Divisions

The brain is composed of six major divisions and each of those divisions can be further subdivided into several anatomically and functionally distinct areas. The six major divisions are the cerebral hemispheres, or the telencephalon; the diencephalon; the midbrain; the pons; the medulla; and the cerebellum. Each of these divisions is found in both hemispheres of the brain, but they may differ in size and shape.

There are a number of important junctions that also help to assist in the delineation and location of anatomical structures and functions. They consist of the cervicomedullary junction between the spinal cord and the medulla, the pontomedullary junction between the medulla and the pons, the pontomesencephalic junction between the pons and the midbrain and the midbrain diencephalic junction between the midbrain and the diencephalon. These important structures will help to determine location of other structures as we proceed.

Slide 9: Orientation and Planes of the Central Nervous System

As we continue our overview in order to understand the language of neuroanatomy, it is important that we also understand the orientation for different directions and planes of the images and specimens we are looking at. As you become more familiar with the vocabulary, the descriptions later in the series will be easier to follow.

In lower animals, (here on the left, we are taking a look at a lizard), the nervous system is in a linear orientation. So the term ventral, from Latin venter, meaning "belly," is always toward the ground. Dorsal, Latin for "back," as in a shark's fin, is toward the back of the animal. Rostral, Latin for "beak," is toward the sky, and caudal, Latin for "tail," is toward the tail. In humans and other higher primates, we have upright posture, and the nervous system makes a bend of approximately 110º. Because of this bend, or flexure at the midbrain diencephalic junction, positional terms are slightly different depending on whether we're above or below the flexure.

For structures above the midbrain, the orientation of the nervous system is the same with respect to the ground, as in reptiles:

Anterior = rostral
Posterior = caudal
Superior = dorsal
Inferior = ventral

Below the level of the midbrain diencephalic junction:

Anterior = ventral
Posterior = dorsal
Superior = rostral
Inferior = caudal

Sometimes the only way to understand the relationship among parts of a three- dimensional object is to slice through it and look at the internal organization. The orientation of components of the CNS within the body is described typically with reference to three sectional planes or axes. When the nervous system is imaged, we can look at the horizontal plane, which is parallel to the floor as if you look out to the horizon. Equivalent terms for horizontal sections are axial and transverse, meaning perpendicular to the long axis of one's body. So we're dividing the body into its superior and inferior portions, again in the horizontal plane. Coronal sections come from the section plane approximating a tiara, like a crown, and would section the body into its front and back halves. And finally, sagittal sections are in the direction of an arrow, shown as if an arrow is going to be shot into the air and sections the body into right and left halves. You can think of an archer or the constellation Sagittarius. Our picture above is demonstrating a sagittal section of the human brain.

Slide 10: Cytology of Neurons

The human brain is a network of more than 100 billion individual nerve cells interconnected in systems that construct our perceptions of the external world, fix our attention and control the machinery of our action. A first step in understanding the mind therefore is to learn how neurons are organized into signaling pathways and how neurons communicate by means of synaptic transmission.

Microscopically, the nervous system is composed of nerve cells called neurons and support cells called glial cells, or simply glia. Neurons are considered the basic functional units of the nervous system and are mainly responsible for signaling and communication in the nervous system, although glial cells may contribute as well. Neural signaling is a complex phenomenon. We're going to present it here in a more simplified manner geared toward our neuroanatomy discussions.

When we look at our glial cells, they are there to separate and protect neurons, provide a supporting framework, have the ability to act as phagocytes, help regulate interstitial fluid composition, and are in greater number than neurons. Some examples of support cells are ependymal cells, which produce CSF; astrocytes, which maintain the blood brain barrier; oligodendrocytes, which form myelin around axons; and microglia, which produce monocytes and macrophages that engulf cellular waste and debris.

Slide 11: Neurons

Here, looking at a neuron structurally, we can see that it's composed of a cell body, varying numbers of dendrites, an axon, and specialized site for communication called synapse.

The cell body or soma contains the nucleus and organelles that provide energy and synthesis organic materials, especially neurotransmitters that are important for cell to cell communication. Extending out from the cell body are dendrites that are highly branched, and each branch has a dendritic spine that receives information from other neurons.

The axon is a long cytoplasmic process that is capable of propagation of an electrical impulse, known as the action potential. The axon may branch along its length producing side branches that enable a single neuron to communicate with several other cells. The main axon trunk and any collaterals end in a series of fine extensions, known as telodendria. Telodendria of an axon end at a synaptic terminal.

Slide 12: Classification of Neurons

Neurons can be classified both structurally by their shape and functionally by the activities that they perform. Structural classifications include anaxonic, bipolar, unipolar, and multipolar. Here, pictured, you can see an anaxonic neuron is small with no features that distinguish axons from dendrites; they are typically located in the brain and special sense organs.

Bipolar neurons have two distinct processes and are a single dendrite and a single axon arising from a cell body. They are rarer, often sensory, and are involved with special senses like sight or smell. Unipolar neurons, also called pseudounipolar, are the axon and dendrite that arise from a single process coming off the cell body. Multipolar, meaning they have several dendrites as well as several axons and often a single axon arising from the cell body, will travel a great distance, and then one or several axon collaterals will branch off the main axon to reach a different target.

When we look at functional classifications, neurons can also be sensory or motor, and then we have interneurons. Sensory neurons, or afferent neurons, deliver information from sensory receptors out in the PNS to the CNS. Motor neurons, or efferent neurons, carry information from the CNS to peripheral effectors in a peripheral tissue or in an organ. And interneurons, which number in the billions, outnumber all other types of neurons combined. They are responsible for the distribution of both sensory and motor activity.

Slide 13: Cellular Communication

All normal neuronal functions depend on events that occur at the cell membrane. There is an electrochemical gradient that is the sum of all electrical and chemical forces, making neuronal communication both electrically and chemically active. When excitatory synaptic inputs combine with the cells electrochemical gradient to excite a neuron, a transient voltage change called an action potential occurs lasting about 1 millisecond. Action potentials can travel rapidly throughout the length of a neuron, propagating at rates up to about 60 meters per second along the cell membrane.

An action potential is a signal passed on through an axon and influences other neurons. An action potential arises when a region of excitable membrane depolarizes to its threshold. The steps that are involved in activation consist of sodium channels, sodium channels inactivation, potassium channel activation, and then the return to normal permeability.

Slide 14: Synapses

An action potential traveling along an axon is considered a nerve impulse. At synapses between two neurons, information can then pass from the presynaptic neuron to the postsynaptic neuron. A synapse is either electrical, having direct physical contact, or chemical, involving a neurotransmitter.

Electrical synapses occur in both the CNS and the PNS, but are rarer in the PNS. At electrical synapses, the presynaptic and postsynaptic membranes are bound by interlocking membrane proteins allowing a passage of local currents. Chemical synapses are more common than electrical. The action potential triggers the release of neurotransmitter molecules from synaptic vesicles, allowing chemical communication with the postsynaptic cell. Excitatory neurotransmitters will cause depolarization and promote the generation of an action potential due to the influx of sodium, whereas inhibitory neurotransmitters cause hyperpolarization and suppress the generation of an action potential.

Axons are often insulated by glial cells (Shwann cells in PNS and oligodendrocytes in the CNS). These will form a special lipid sheath around the axon, thereby increasing the rate of action potential conduction. Voltage gated ion channels are concentrated in short exposed segments of the axon called the Nodes of Ranvier. Conduction from node to node occurs rapidly by a process called saltatory conduction.

Slide 15: Chemical Neurotransmission

When looking at chemical neurotransmitters, it is important to note that they have two general types of functions. One is to mediate rapid communication between neurons through fast excitatory or inhibitory electrical events known as excitatory postsynaptic potentials (EPSP) or inhibitory postsynaptic potentials (IPSP). Fast EPSPs and IPSPs occur on a time scale of tens of milliseconds, and rapidly move the membrane voltage of a postsynaptic neuron between states more or less likely to fire an action potential. The postsynaptic neuron can summate EPSPs and IPSPs arising from many presynaptic inputs. The second function of a chemical neurotransmitter is neuromodulation, generally occurring over a slower time scale.

Neuromodulation includes a broader range of cell mechanisms involving signaling cascades that regulate synaptic transmission, neuronal growth, and other functions. Neuromodulation can either facilitate or inhibit the subsequent signaling properties of a neuron.

Here we have some examples of neurotransmitters and their function in the nervous system. Norepinephrine is typically excitatory. It is also known as noradrenaline in sympathetic functions. Dopamine is involved primarily in the midbrain and may be excitatory or inhibitory. Inhibitory effects are thought to play a role in precise movement control, can prevent overstimulation of neurons that control skeletal muscle tone, and, if damaged, will produce parkinsonism. Serotonin is involved in the entire CNS. Inadequate amounts are thought to have widespread effects on a person's attention and emotional states and is thought to be responsible for depression. Glutamate is an excitatory neurotransmitter in the entire CNS. GABA or gamma amino-butyric acid is an inhibitory neurotransmitter in the entire CNS. Acetylcholine is involved with muscle contraction at nicotinic receptors, as well as autonomic functions: preganglionic (nicotinic) and parasympathetic muscarinic receptors. Histamine is involved in the entire CNS. It's an excitatory neuromodulator. Glycine is inhibitory at the spinal cord. And many peptides, or neuropeptides, will perform neuromodulatory functions for the entire CNS.

Slide 16: CNS Gray Matter and White Matter

The CNS, in dissection areas made up of mostly myelinated axons, will appear glossy white primarily because of the lipids within the myelin, which we call white matter. These axons have the ability to transmit signals over long distances. Areas containing mostly neuron cell bodies, dendrites, and unmyelinated axons constitute the gray matter where much of our synaptic communication occurs between neurons.

The surfaces of the cerebral hemispheres are a unique example of a mantle of gray matter, which conveys signals to and from the cortex. Gray matter can also be found in large clusters of cells called nuclei, located deep within the cerebral hemispheres and brainstem. Examples include basal ganglia, thalamus, and cranial nerve nuclei.

In the cerebral hemispheres, the gray matter cortex is outside while the white matter is in deep. In the spinal cord the opposite is true; white matter pathways lie on the outside while gray matter is in the center. In the brainstem, gray matter and white matter regions are found both inside and outside, although most of the outside surface is white matter.

Several different names with similar meaning are used for white matter pathways in the CNS, including tract, fascicle, lemniscus, and bundle. If the white matter pathway connects identical structures on the right and left side of the brain or CNS, it is called a commissure. Axons in the PNS form bundles called peripheral nerves. Nerves and clusters of cell bodies in the PNS are called ganglia.

Slide 17: Spinal Cord and Peripheral Nervous System

The adult spinal cord, pictured here, measures about 45 cm in length and has a maximum width of about 14 mm. In the spinal cord, white matter pathways again lie on the outside while gray matter is in the center. We can see this depicted by the gray matter horns in the central area of the cord. The spinal cord also has localized enlargements, which provide innervation to the limbs. These enlargements are named according to the level they exit the bony vertebral bodies, for example, cervical, thoracic, lumbar, and sacral.

Throughout the nervous system, motor systems tend to be more ventral or anterior, and sensory systems appear to be more dorsal or posterior. And the same holds true for the spinal cord. Thus, dorsal nerve roots bring afferent sensory information into the dorsal spinal cord, while ventral nerve roots carry mainly efferent motor signals from the ventral spinal cord to the periphery.

Distal to each dorsal root ganglia, (remember ganglia is a collection of cell bodies), the sensory and motor nerve roots join together in a single spinal nerve (pictured above). Spinal nerves are classified as mixed nerves-that is, they contain both afferent information or sensory, carried in the dorsal root, and efferent, or motor information, carried in the ventral root.

Slide 18: Regions of the Spinal Cord

When looking at the regions of the spinal cord, there are 31 segments and 31 pairs of spinal nerves, each named according to the level they exit the bony vertebral bodies. Yellow depicts cervical; blue, thoracic; red, lumbar; and green, sacral.

If we look at the cord itself, you can see that it is not as long as the vertebral column because, during development, the bony vertebral canal increases in length faster than the spinal cord. Therefore, the spinal cord ends at the level of the first or second lumbar vertebral bones (L1 or L2). Below this level, the spinal canal contains a collection of nerve roots, known as the cauda equina or "horse's tail," which continue down to the exit points.

The sensory and motor nerve roots join together a short distance outside the spinal cord and form mixed sensory and motor spinal nerves as we have seen in the prior slide. In segments controlling skeletal musculature of the neck, upper limbs, and lower limbs, the distribution pattern of dorsal and ventral roots is more complicated. Because control of the arms and legs requires much more signal flow, the nerves controlling the extremities give rise to elaborate mesh works, referred to as nerve plexus. The four major plexus are:
  1. The cervical plexus, innervating the muscles of the neck
  2. The brachial plexus, for the upper extremity
  3. The lumbar and sacral plexus, for the lower extremity and pelvis
In addition, the spinal cord contains relatively increased amounts of gray matter in these segments causing the overall thickness of the cord to be greater. These regions of the cord are called the cervical enlargements and the lumbosacral enlargements respectively. Slide 19: The Autonomic Nervous System

In addition to the sensory and motor pathways already described, the PNS includes some specialized neurons that are involved in coordinating automatic functions such as heart rate, peristalsis, sweating, and smooth muscle contraction in the walls of blood vessels, bronchi, sex organs, and pupils as examples. These neurons are part of the autonomic nervous system, pictured on the slide.

The autonomic nervous system has two major divisions. On the left, the sympathetic division, as you can see, arises from the thoracic and lumbar spinal levels T1-L2, and is therefore called the thoracolumbar division. It releases the neurotransmitter norepinephrine onto its end organs, and is involved in "fight or flight" functions such as increased heart rate, increased blood pressure, bronchodilation of the lung, and increased pupil size. On the right, the parasympathetic division arises from the cranial nerves and from the sacral spinal levels S2 to S4, and hence is called the craniosacral division. It releases the neurotransmitter acetylcholine onto end organs, and is involved in more sedentary functions or "rest and repose" functions, such as increasing gastric secretions and peristalsis, slowing down the heart rate and decreasing pupil size.

Slide 20: Cerebral Cortex

The adult brain contains almost 98% of the body's neural tissue and typically weighs about 1.4kg. It is dominated in size by the cerebrum and can be divided at midline into right and left halves. The right and left halves are separated by a deep longitudinal fissure. The term "fissure" is used to refer to deep sulci. The cerebral cortex is not smooth and forms a series of elevated ridges called gyri, which is plural, or gyrus, which is singular. The gyri are separated by infolding depressions or crevices called sulci. The cerebral hemispheres have four major lobes. The frontal lobe here in brown, the temporal lobe in blue, the parietal lobe in purple, and the occipital lobe in green. The frontal lobes are located in the front of the brain and extend back to a landmark called the central sulcus, which is a deep groove that separates the frontal lobe from the more posterior parietal lobe. The frontal lobes are also separated from the temporal lobe by another deep sulcus called the lateral or sylvian fissure. The parietal lobes are bounded anteriorly by the central sulcus but have no sharp demarcation from the temporal lobes or the occipital lobes when viewed from the lateral side of the brain. When viewed from the medial aspect, here on the right, the parietal-occipital sulcus can be seen more easily, separating the parietal lobe from the occipital lobes. A large C-shaped band of white matter, called the corpus callosum (meaning "hard body") interconnects the right and left cerebral hemispheres and permits communication. The corpus callosum alone contains more than 200 million axons, carrying some 4 billion impulses per second.

Slide 21: Surface Anatomy

Although there is some variability, the sulci and gyri of the cerebral hemispheres form certain fairly consistent patterns. Let's now review the name of the major sulci, gyri and other structures of the cerebral hemispheres. Functions of these hemispheres and lobes will be discussed in the upcoming sections.

Here on the lateral surface, the frontal lobe, again, is bounded posteriorly by the central sulcus. The gyrus running in front of the central sulcus is called the Precentral gyrus.

The most anterior portion of the parietal lobe is the Postcentral gyrus, lying just posterior to the central sulcus. The Intraparietal sulcus divides the superior parietal lobe from the inferior parietal lobe.

Slide 22: Surface Anatomy (Cont.)

On the medial surface of the brain, the corpus callosum is clearly visible. It consists of the rostrum, toward the nose, the genu where it bends, the body and the splenium. The cingulate gyrus (cingulum meaning "girdle" or "belt") surrounds the Corpus callosum. The portion of the medial occipital lobe below the calcarine fissure is called the Lingula (meaning "little tongue"), while the portion above the calcarine fissure is called the Cuneus (meaning "wedge"). Just in front of the cuneus, the medial parietal lobe is called the Precuneus.

Slide 23: Primary Sensory and Motor Areas

The primary sensory and motor areas are shown here. The precentral gyrus of the frontal lobe forms the anterior border of the central sulcus. The surface of this gyrus is the primary motor cortex, here in red. Neurons of the primary motor cortex direct voluntary movement to the opposite side of the body. The postcentral gyrus of the parietal lobe, here in blue, forms the posterior border of the central sulcus and its surface contains the primary sensory cortex. Neurons in this region receive somatic sensory information from receptors for touch, pressure, pain, vibration and temperature. Note, as in the spinal cord, motor areas lie anterior to somatosensory areas. Sensations of sight, smell and sound arrive at other areas of the cortex. The primary visual cortex receives information about vision and is located in the occipital lobes along banks of a deep sulcus called the calcarine fissures. The primary auditory cortex is on the superior surface of each temporal lobe and receives information about hearing. Higher order motor and sensory information processing takes place in association cortex areas that we will discuss later.

Slide 24: The Motor or Sensory Homunculus

Our ability to localize sensation and motor function to determine precisely where in the body a specific stimulus originates are due to the fact that our sensory and motor pathways are topographically organized. This means that adjacent areas on the receptive surface are mapped to adjacent fibers in white matter pathways and to adjacent regions of the cortex. For example, in the primary motor and primary somatosensory cortex, regions representing the hand are adjacent to regions representing the arm and so on. These somatotopic maps on the cortex are sometimes called the motor and sensory homunculus, or "little man". We can see the sensory homunculus on the left and the motor homunculus on the right, and the representation of our body.

Slide 25: Cell Layers of the Cerebral Cortex

The majority of the cerebral cortex is composed of the neocortex, which has 6 cell layers, labeled I through VI counting from the inward surface. In a few regions such as the limbic system, less than 6 layers are present. Neocortical circuitry is very complex, and we will describe only a few of the major connections of each layer here. Layer I, the molecular layer, contains mainly dendrites of neurons from deeper layers and axons. Layer II, the small pyramidal layer, and layer III, the medium pyramidal layer, contain neurons that project mainly to other areas of the cortex. Layer IV, the granular layer, receives the majority of inputs from the thalamus. Layer V, the large pyramidal layer, projects mostly to subcortical structures other than the thalamus, such as the brainstem, spinal cord, and the basal ganglia. Layer VI, the polymorphic layer, projects primarily to the thalamus. In addition to these connections, numerous other circuits exist between and within the cortical layers that are really beyond the scope of this discussion. The relative thickness of the cell layers will vary as well according to the main function of that area of the cortex. For example, the primary motor cortex has large efferent projections to the brainstem and spinal cord, which control movement. It receives relatively little direct sensory information from thalamic relay centers. Therefore, in the primary motor cortex, layer V is thicker and has many more cell bodies than layer IV.

Slide 26: Brodmann's Cytoarchitectonic Areas

Early in the 20th century, many researchers attempted to describe and classify regional differences in the histological organization of the cerebral cortex. They hoped to correlate the patterns of cell organization with specific functions. The most widely known of these was a cortical map published by Korbinian Brodmann in 1909. On the basis of microscopic studies, Brodmann parceled the cortex into 52 cytoarchitectonic areas, each assigned a number corresponding to the order in which he prepared the slides. It turns out that many of the areas identified by Brodmann correlate fairly well with various functional areas of the cortex, and therefore his nomenclature is still used today. Brodmann area 44, for example, corresponds to the speech center, Brodmann area 41, to the auditory cortex, and Brodmann area 4 follows the contours of the primary motor cortex.

Slide 27: Motor Systems

Motor control involves a delicate balance between multiple parallel pathways and recurrent feedback loops. Let's look at an overview of the most important motor pathways, and of the cerebellar and basal ganglia, which are major feedback loops.

The most important motor pathway in humans is the corticospinal tract. The corticospinal tract begins mainly in the primary motor cortex, where the neuron cell bodies project via axons down through the cerebral white matter and the brainstem to reach the spinal cord. The majority of the fibers in the corticospinal tract (about 85%) cross over to control movement on the opposite side of the body. The crossing over, known as the pyramidal decussation, occurs at the junction between the medulla and the spinal cord. Lesions, occurring above the pyramidal decussation, will produce contralateral, or opposite side weakness with respect to the lesion, while lesions below the pyramidal decussation will produce ipsilateral, or same-sided weakness. Several other descending motor pathways that exist in addition to corticospinal tract will be discussed later.

Motor neurons that project from the cortex down to the spinal cord or brainstem are referred to as upper motor neurons (UMNs). UMNs form synapses onto lower motor neurons (LMNs), which are located in the anterior horns of the central gray matter of the spinal cord or in the brainstem nuclei. The axons of LMNs project out of the CNS via the anterior spinal roots or via the cranial nerves to finally reach muscle cells in the periphery. Lesions affecting UMNs and LMNs have certain clinically distinct features which we will discover later.

Slide 28: Motor Systems (Cont.)

The motor system is called upon to perform many delicate and complicated tasks. Therefore, in order to refine the output of the motor system, multiple feedback systems are used including the cerebellum and the basal ganglia. These two systems do not exert direct control over lower motor neurons. Instead, the cerebellum and the basal ganglia act by modulating the output of the corticospinal tract and other descending motor systems. The cerebellum and the basal ganglia both receive major inputs from the motor cortex. The cerebellum also receives significant inputs from the brainstem and the spinal cord. The cerebellum and basal ganglia in turn project back to the motor cortex via the thalamus. Lesions in the basal ganglia cause hypokinetic movement disorders, such as parkinsonism, in which movements are infrequent, slow, and rigid; and hyperkinetic movement disorders such as Huntington's disease, which are characterized by dance-like involuntary movements.

Slide 29: Somatosensory Systems

Sensation from the body is conveyed by parallel pathways mediating different sensory modalities that travel to the central nervous system. Let's review the most important sensory pathways and introduce the thalamus, a major relay center for signals of all kinds that travel to the cerebral cortex. Somatic sensation refers to the conscious perception of touch, pain, temperature, vibration and proprioception. There are two main pathways, pictured here, in the spinal cord for somatic sensation.
  1. On the left, the posterior column pathway carries sensation of highly localized proprioception, vibration sense, and fine discriminative touch.
  2. On the right, the anterolateral pathway provides conscious sensation of poorly localized crude touch, pain, and temperature sense.
Some aspects of touch are carried by both pathways, so touch sensation is not eliminated in isolated lesions of either pathway. Note that the primary sensory neurons of cell bodies are located outside the CNS in the dorsal root ganglion and they have bifurcating axons, with one long process extending into the periphery and another into the spinal cord. Equally as important as the knowledge of the corticospinal tract crossing over at the pyramidal decussation, which allows us to localize lesions, is the knowledge of where in the CNS the two main sensory pathways cross over. The posterior column carries information about proprioception, vibration sense,and fine touch; it first enters the spinal cord via the dorsal root and then the ipsilateral white matter, or, alternatively, dorsal column to ascend all the way to the dorsal column nuclei in the medulla. It is here that they make a synapse onto secondary sensory neurons, which send out axons that cross over to the other side of the medulla. These axons continue to ascend, now on the contralateral side, and synapse in the thalamus; from there the neurons are going to project to the primary somatosensory cortex in the postcentral gyrus.

The anterolateral pathway carries information about pain, temperature, sense, and crude touch; it enters the cord via the dorsal roots. However, these axons make their first synapses immediately in the gray matter of the spinal cord. Axons from the secondary sensory neurons cross over to the other side of the spinal cord and ascend in the anterolateral white matter, forming the spinothalamic tract. After synapsing in the thalamus, the pathway again continues to the primary somatosensory cortex.

The thalamus is an important relay center. Nearly all pathways that project to the cerebral cortex do so after synapsing in the thalamus. The thalami are gray matter structures located deep within the cerebral white matter just above the brainstem and behind the basal ganglia, pictured above. They are shaped somewhat like eggs, with their posterior ends angled outward, together forming an inverted V in horizontal sections.

Each sensory modality, including vision, hearing, taste, and somatic sensation, has a different nuclear area where synapses occur before the information is relayed to the cortex. Non-sensory pathways also relay in the thalamus. For example, there are thalamic nuclei that process information coming from the basal ganglia and the cerebellum, and limbic pathways and brainstem formation on the way to the cortex. An important feature of thalamic circuits is the reciprocal nature of the cortical-thalamic connections. Thus, virtually all the cortical regions project strongly via layer VI back to thalamic areas from which their major inputs arise. Slide 30: Stretch Reflex

The monosynaptic stretch reflex is a well studied reflex arc that provides rapid local feedback for motor control. The reflex arc begins with specialized receptors called muscle spindles, pictured here, which detect the amount and rate of stretch in muscle. This information is then transmitted to the distal process of sensory neurons and is then conveyed via the dorsal root into the spinal gray matter. In the spinal gray matter, the sensory neurons form multiple synapses, including some direct synapses onto LMNs that are located in the anterior horn cells. The LMNs project via the ventral roots back out to the muscle, causing it to contract. Damage anywhere in this pathway can cause the reflex to be diminished or absent.

In addition to monosynaptic pathways, the afferent sensory neuron forms synapses onto excitatory and inhibitory interneurons in the spinal gray matter, which in turn make synapses onto LMNs. Thus, local circuits in the spinal cord can use sensory information to regulate the activity of LMNs without conscious input of higher centers. There are some descending pathways that modulate this activity of the stretch reflex. As we will learn, if these higher centers or their descending pathways are damaged, the stretch reflex can become hyperactive or hypoactive. By testing the stretch reflex on the neurologic exam, you can obtain information about multiple pathways, including the sensory neurons and the motor neurons in the PNS, and the descending modulatory pathways in the CNS. Since the stretch reflex is often tested on neurologic exam by tapping over a tendon with a reflex hammer, this is commonly called a deep tendon reflex, or DTR.

Slide 31: Brainstem and Cranial Nerves

The overall structure of the brainstem can be seen here. It is composed of the midbrain, the pons, and the medulla. The brainstem is connected to the diencephalon rostrally, the cerebellum dorsally, and the spinal cord caudally.

Cranial nerves are peripheral nervous system components that connect directly to the brain. There are 12 pairs of cranial nerves and they are visible on the ventrolateral surface of the brainstem; and each has a name relative to its appearance or to its function. The cranial nerves are analogous in some way to spinal nerves, having both sensory and motor functions. However, they also carry out more specialized functions relating to the organs of the head. Examination of the cranial nerves will provide you crucial information about the function of the nervous system, which we will discuss in more detail later.

Slide 32: Brainstem Nuclei

In addition to cranial nerve nuclei and pathways, the brainstem is also packed with numerous other important nuclei and white matter tracts. All information passing between the cerebral hemispheres and the spinal cord must pass through the brainstem. Therefore, lesions in the brainstem can have a devastating effect on both sensory and motor function.

An important region of the brainstem contains many of these nuclei is the reticular formation. It's named for the network-like appearance of its fibers in histological sections. The reticular formation extends throughout the central portions of the brainstem from the medulla to the midbrain. The more caudal portions of the reticular formation in the medulla and the lower pons tend to be more involved in motor and autonomic functions.

The rostral reticular formation in the upper pons and midbrain play an important role in regulating level of consciousness, influencing higher areas mainly through modulation of thalamic activity. Therefore, lesions that affect the pontomesencephalic reticular formation can cause lethargy and coma.

Slide 33: Limbic System

The limbic system is composed of several structures in the brain because they are located near the medial edge or fringe ("limbus" in Latin) of the cerebral cortex. These structures have evolved from a system devoted mainly to olfaction in simpler animals to perform diverse functions, including regulation of your emotions, memory, appetite drives, and anautonomic and neuroendocrine control.

The limbic system includes certain cortical areas located in the medial and anterior temporal lobes, the anterior insula, inferior medial frontal lobes, and the cingulate gyrus. It also includes deeper structures such as the hippocampal formation and the amygdale located in the medial temporal lobes, several nuclei in the medial thalamus, hypothalamus, basal ganglia, septal area, and brainstem. These areas are all interconnected by a variety of pathways, including the fornix, a paired arch-shaped white matter structure that connects the hippocampal formation to the hypothalamus, and the septal nuclei.

Lesions in the limbic system can cause deficits in the consolidation of immediate recall into long term memories. Thus, patients with lesions in these areas may have not trouble recalling remote events, but they might have difficulty forming new memories. In addition, limbic dysfunction can cause behavioral changes that may underlie a number of psychiatric disorders. Finally, epileptic seizures most commonly arise from the limbic structures of the medial temporal lobe, resulting in seizures that may begin with emotions such as fear, memory distortions such as déjà vu, or olfactory hallucinations.

Slide 34: Association Cortex

The primary sensory and motor regions of the cerebral cortex are connected to nearby association areas. Association areas help the primary cortex interpret incoming data or to coordinate a motor response. Association areas that handle a single sensory or motor modality are called unimodal. Unimodal association areas are usually located adjacent to the primary motor or primary sensory area they're responsible for. For example, the premotor and supplementary motor association areas are adjacent to the primary motor cortex located in the sagittal view. Heteromodal association cortex areas are involved in integrating functions from multiple sensory and/or multiple motor modalities. It's important that we take a brief review of the functions of a few clinically important association areas especially since we will learn how to examine these structures in the mental status exam.

Language usually is perceived first by the primary auditory cortex in the superior temporal lobe when we are listening to speech; language is perceived in the primary visual cortex in the occipital lobe when we are reading. From here, cortical-to-cortical association fibers will convey information to a unique association area, Wernicke's area, which is located in the dominant hemisphere for language (usually the left hemisphere). Damage or lesions to Wernicke's area cause deficits in language comprehension, also sometimes called receptive or sensory aphasia or Wernicke's aphasia. Broca's area is located on the frontal lobe, also in the left hemisphere adjacent to the areas of primary motor cortex involved with moving the lips, tongue, face and larynx. Lesions in Broca's area cause deficits in the production of language, with relative sparing of language comprehension. This is called expressive or motor's aphasia, or Broca's aphasia, which can be remembered by the mnemonic "Broca's broken boca" (boca meaning "mouth" in Spanish).

So here we're seeing that association areas are important in assisting primary motor or primary sensory areas in interpreting information or coordinating motor responses.

Slide 35: Blood Supply to the Brain

When looking at blood supply to the brain, there are two major arteries that carry all of the blood to the brain and one pair of veins. The internal carotid arteries form the anterior blood supply. The vertebral arteries, which join together with a single basilar artery, form the posterior blood supply. The anterior and posterior blood supplies from the carotid and the vertebrobasilar systems join together in an anastomotic ring at the base of the brain called the Circle of Willis. The main arteries supplying the cerebral hemispheres will arise from the Circle of Willis. Ordinarily, however, the anterior and middle cerebral arteries derive their main blood supply from the internal carotid arteries, while the posterior cerebral arteries derive their main supply from the vertebrobasilar system. The main arteries supplying the brainstem and the cerebellum also arise from the vertebral and basilar arteries. These include the superior, anterior, inferior, and posterior inferior cerebellar arteries. Venous drainage for the brain is provided almost entirely by the internal jugular veins.

Slide 36: Blood Supply to the Spinal Cord

The spinal cord receives its blood supply from the anterior spinal artery, which runs along the ventral surface of the cord in the midline and from the paired posterior spinal arteries, running along the right and left dorsal surface of the cord. The anterior and posterior spinal arteries are supplied in the cervical region mainly by branches arising from the vertebral arteries. In the thoracic and lumbar regions, the spinal arteries are supplied by radicular arteries arising from the aorta.

Slide 37: Conclusion

In this slide series, we have reviewed overall structure and organization of the nervous system. We have discussed, in general terms, the functions of each of the main areas of the brain, spinal cord, and PNS and briefly reviewed the blood supply to the brain. This overview should provide a framework upon which important details will be filled in and reinforced throughout the following lecture series.