• White Matter vs.

Gray Matter
• The Meninges
• Cerebrospinal Fluid
• Blood-Brain Barrier
The Human •
•
The Spinal Cord
The Hindbrain
Central Nervous o Medulla oblongata
o Pons
System •
o Cerebellum
The Midbrain
The central nervous system is made up of • The Forebrain
o Diencephalon
the
o The Cerebral Hemispheres
• spinal cord and • Mapping the Functions of the Brain
• brain • The Electroencephalograph (EEG)
• Phineas P. Gage
The spinal cord • Stimulating the brain with electrodes
• Tomography
• conducts sensory information • Magnetic Resonance Imaging
from the peripheral nervous
system (both somatic and • Magnetoencephalography (MEG)
autonomic) to the brain
• conducts motor information from the brain to our various effectors
o skeletal muscles
o cardiac muscle
o smooth muscle
o glands
• serves as a minor reflex center

The brain

• receives sensory input from the spinal cord as well as from its own nerves (e.g., olfactory
and optic nerves)
• devotes most of its volume (and computational power) to processing its various sensory
inputs and initiating appropriate — and coordinated — motor outputs.

White Matter vs. Gray Matter

Both the spinal cord and the brain consist of

• white matter = bundles of axons each coated with a sheath of myelin

• gray matter = masses of the cell bodies and dendrites — each covered with synapses.

In the spinal cord, the white matter is at the surface, the gray matter inside.

In the brain of mammals, this pattern is reversed. However, the brains of "lower" vertebrates like
fishes and amphibians have their white matter on the outside of their brain as well as their spinal
cord.
The Meninges
Both the spinal cord and brain are covered in three continuous sheets of connective tissue, the
meninges. From outside in, these are the

• dura mater — pressed against the bony surface of the interior of the vertebrae and the
cranium
• the arachnoid
• the pia mater

The region between the arachnoid and pia mater is filled with cerebrospinal fluid (CSF).

The Extracellular Fluid (ECF) of the Central Nervous

System
The cells of the central nervous system are bathed in a fluid that differs from that serving as the
ECF of the cells in the rest of the body.

• The fluid that leaves the capillaries in the brain contains far less protein than "normal"
because of the blood-brain barrier, a system of tight junctions between the endothelial
cells of the capillaries. This barrier creates problems in medicine as it prevents many
therapeutic drugs from reaching the brain.
• cerebrospinal fluid (CSF), a secretion of the choroid plexus. CSF flows uninterrupted
throughout the central nervous system
o through the central cerebrospinal canal of the spinal cord and
o through an interconnected system of four ventricles in the brain.

CSF returns to the blood through veins draining the brain.

The Spinal Cord

31 pairs of
spinal nerves
arise along the
spinal cord.
These are
"mixed" nerves because each contain both sensory and motor axons. However, within the spinal
column,

• all the sensory axons pass into the dorsal root ganglion where their cell bodies are
located and then on into the spinal cord itself.
• all the motor axons pass into the ventral roots before uniting with the sensory axons to
form the mixed nerves.

The spinal cord carries out two main functions:

• It connects a large part of the peripheral nervous system to the brain. Information (nerve
impulses) reaching the spinal cord through sensory neurons are transmitted up into the
brain. Signals arising in the motor areas of the brain travel back down the cord and leave
in the motor neurons.
• The spinal cord also acts as a minor coordinating center responsible for some simple
reflexes like the withdrawal reflex.

The interneurons carrying impulses to and from specific receptors and effectors are grouped
together in spinal tracts.

Crossing Over of the Spinal Tracts

Impulses reaching the spinal cord from the left side of the body eventually pass over to tracts
running up to the right side of the brain and vice versa. In some cases this crossing over occurs as
soon as the impulses enter the cord. In other cases, it does not take place until the tracts enter the
brain itself.

The Human Brain

The brain of all vertebrates develops from three swellings at the anterior end of the neural canal
of the embryo. From front to back these develop into the

• forebrain (also known as the prosencephalon)

• midbrain (mesencephalon)
• hindbrain (rhombencephalon)

The brain receives nerve impulses from

• the spinal cord and

• 12 pairs of cranial nerves
o Some of the cranial nerves are "mixed", containing both sensory and motor axons
o Some, e.g., the optic and olfactory nerves (numbers I and II) contain sensory
axons only
o Some, e.g. number III that controls eyeball muscles, contain motor axons only.
The Hindbrain
The main structures of
the hindbrain
(rhombencephalon) are
the

• medulla
oblongata
• pons and
• cerebellum

Medulla oblongata

The medulla looks like a swollen tip to the spinal cord. Nerve impulses arising here

• rhythmically stimulate the intercostal muscles and diaphragm — making breathing

possible
• regulate heartbeat
• regulate the diameter of arterioles thus adjusting blood flow.

The neurons controlling breathing have mu (µ) receptors, the receptors to which opiates, like
heroin, bind. This accounts for the suppressive effect of opiates on breathing. Destruction of the
medulla causes instant death.

Pons

The pons seems to serve as a relay station carrying signals from various parts of the cerebral
cortex to the cerebellum. Nerve impulses coming from the eyes, ears, and touch receptors are
sent on the cerebellum. The pons also participates in the reflexes that regulate breathing.

The reticular formation is a region running through the middle of the hindbrain (and on into the
midbrain). It receives sensory input (e.g., sound) from higher in the brain and passes these back
up to the thalamus. The reticular formation is involved in sleep, arousal (and vomiting).

Cerebellum

The cerebellum consists of two deeply-convoluted hemispheres. Although it represents only 10%
of the weight of the brain, it contains as many neurons as all the rest of the brain combined.
Its most clearly-understood function is to coordinate body movements. People with damage to
their cerebellum are able to perceive the world as before and to contract their muscles, but their
motions are jerky and uncoordinated.

So the cerebellum appears to be a center for learning motor skills (implicit memory).
Laboratory studies have demonstrated both long-term potentiation (LTP) and long-term
depression (LTD) in the cerebellum.

The Midbrain
The midbrain (mesencephalon) occupies only a small region in humans (it is relatively much
larger in "lower" vertebrates). We shall look at only three features:

• the reticular formation: collects input from higher brain centers and passes it on to
motor neurons.
• the substantia nigra: helps "smooth" out body movements; damage to the substantia
nigra causes Parkinson's disease.
• the ventral tegmental area (VTA): packed with dopamine-releasing neurons that
o are activated by nicotinic acetylcholine receptors and
o whose projections synapse deep within the forebrain.

The VTA seems to be involved in pleasure: nicotine, amphetamines and cocaine bind to
and activate its dopamine-releasing neurons and this may account — at least in part (see
below)— for their addictive qualities.

The midbrain along with the medulla and pons are often referred to as the "brainstem".

The Forebrain
The human forebrain (prosencephalon) is made up of

• a pair of large cerebral hemispheres, called the telencephalon. Because of crossing over
of the spinal tracts, the left hemisphere of the forebrain deals with the right side of the
body and vice versa.
• a group of unpaired structures located deep within the cerebrum, called the
diencephalon.
Diencephalon

We shall consider 4 of its structures: the

• Thalamus.
o All sensory input (except for olfaction) passes through it on the way up to the
somatic-sensory regions of the cerebral cortex and then returns to it from there.
o signals from the cerebellum pass through it on the way to the motor areas of the
cerebral cortex.
• Lateral geniculate nucleus (LGN). All signals entering the brain from the optic
nerves enter the LGN and undergo some processing before moving on the
various visual areas of the cerebral cortex.

• Hypothalamus.
o The seat of the autonomic nervous system. Damage to the hypothalamus is
quickly fatal as the normal homeostasis of body temperature, blood chemistry, etc.
goes out of control.
o The source of 8 hormones, two of which pass into the posterior lobe of
the pituitary gland.

• Posterior lobe of the pituitary.

Receives
o antidiuretic hormone (ADH) and
o oxytocin

from the hypothalamus and releases them into the blood.

The Cerebral Hemispheres

Each hemisphere of the cerebrum is
subdivided into four lobes visible from the
outside:

• frontal
• parietal
• occipital
• temporal

Hidden beneath these regions of cerebral

cortex are the
 • olfactory bulbs; they receive input from the olfactory epithelia.

• striatum; it receives input from the frontal lobes and also from the limbic system
(below). At its base is the
• nucleus accumbens (NA).

The pleasurable (and

addictive) effects of
amphetamines, cocaine,
and perhaps other
psychoactive drugs seem to
depend on their producing
increasing levels of
dopamine at the synapses
in the nucleus accumbens
(as well as the VTA).

limbic system; it receives input from various association areas in the cerebral cortex and
passes signals on to the nucleus accumbens. The limbic system is made up of the:

o hippocampus. It is essential for the formation of long-term memories.

o amygdala

The amygdala appears to be a center of emotions (e.g., fear). It sends signals to

the hypothalamus and medulla which can activate the flight or fight response of
the autonomic nervous system.

In rats, at least, the amygdala contains receptors for

 vasopressin whose activation increases aggressiveness and other signs of

the flight or fight response;
 oxytocin whose activation lessens the signs of stress.

The amygdala receives a rich supply of signals from the olfactory system, and this
may account for the powerful effect that odor has on emotions (and evoking
memories).

Mapping the Functions of the Brain

It is estimated that the human brain contains 100 billion (1011) neurons averaging 10,000
synapses on each; that is, some 1015 connections. How to unravel the workings of such a
complex system?

Several methods have been useful.

Histology

Microscopic examination with the aid of selective stains has revealed many of the physical
connections created by axons in the brain.

The Electroencephalograph (EEG)

This device measures electrical activity (brain "waves") that can be detected at the surface of the
scalp. It can distinguish between, for example, sleep and excitement. It is also useful in
diagnosing brain disorders such as a tendency to epileptic seizures.

Damage to the Brain

Many cases of brain damage from, for example,

• strokes (interruption of blood flow to a part of the brain)

• tumors in the brain
• mechanical damage (e.g., bullet wounds)

have provided important insights into the functions of various parts of the brain.

Example 1:

Battlefield injury to the left temporal lobe of the cerebrum interferes with speech.

Example 2: Phineas P. Gage

In 1848, an accidental explosion drove a metal bar

completely through the frontal lobes of Phineas P.
Gage. Not only did he survive the accident, he
never even lost consciousness or any of the
clearly-defined functions of the brain. However,
over the ensuing years, he underwent a marked
change in personality. Formerly described as a
reasonable, sober, conscientious person, he
became — in the words of those observing him —
"thoughtless, irresponsible, fitful, obstinate, and profane". In short, his personality had changed,
but his vision, hearing, other sensations, speech, and body coordination were unimpaired.
(Similar personality changes have since been often observed in people with injuries to their
prefrontal cortex.)
The photograph (courtesy of the Warren Anatomical Museum, Harvard University Medical
School) shows Gage's skull where the bar entered (left) and exited (right) in the accident (which
occurred 12 years before he died of natural causes in 1861).

Stimulating the exposed brain with electrodes

There are no pain receptors on the surface of the brain,

and some humans undergoing brain surgery have
volunteered to have their exposed brain stimulated with
electrodes during surgery. When not under general
anesthesia, they can even report their sensations to the
experimenter.

Experiments of this sort have revealed a band of cortex

running parallel to and just in front of the fissure of
Rolando that controls the contraction of skeletal
muscles. Stimulation of tiny spots within this motor
area causes contraction of the muscles.

The area of motor cortex controlling a body part is not

proportional to the size of that part but is proportional to
the number of motor neurons running to it. The more motor neurons that activate a structure, the
more precisely it can be controlled. Thus the areas of the motor cortex controlling the hands and
lips are much larger than those controlling the muscles of the torso and legs.

A similar region is located in a parallel band of cortex just behind the fissure of Rolando. This
region is concerned with sensation from the various parts of the body. When spots in this
sensory area are stimulated, the patient reports sensations in a specific area of the body. A map
can be made based on these reports.

When portions of the occipital lobe are stimulated electrically, the patient reports light.
However, this region is also needed for associations to be made with what is seen. Damage to
regions in the occipital lobe results in the person's being perfectly able to see objects but
incapable of recognizing them.

The centers of hearing — and understanding what is heard — are located in the temporal lobes.

Diagnostics:

1. CT = X-ray Computed Tomography

This is an imaging technique that uses a series of x-ray exposures taken from different angles.
Thanks to computers, these can be integrated to produce a picture of the brain. CT scanning is
routinely used to quickly diagnose strokes.

2. PET = Positron-Emission Tomography

This imaging technique requires that the subject be injected with a radioisotope that emits
positrons.

• water labeled with oxygen-15

(H215O) is used to measure
changes in blood flow (which
increases in parts of the brain
that are active). The short half-
life of 15O (2 minutes) makes it
safe to use.
• deoxyglucose labeled with
fluorine-18. The brain has a voracious appetite for glucose (although representing only
~2% of our body weight, the brain consumes ~20% of the energy produced by cellular
respiration when we are at rest). When supplied with deoxyglucose, the cells are tricked
into taking in this related molecule and phosphorylating it in the first step of glycolysis.
But no further processing occurs so it accumulates in the cell. By coupling a short-lived
radioactive isotope like 18F to the deoxyglucose and using a PET scanner, it is possible to
visualize active regions of the brain.

The images above (courtesy of Michael E. Phelps from Science 211:445, 1981) were produced in
a PET scanner. The dark areas are regions of high metabolic activity. Note how the metabolism
of the occipital lobes (arrows) increases when visual stimuli are received.

Similarly, sounds increase the rate of deoxyglucose uptake in the speech

areas of the temporal lobe.

The image on the right (courtesy of Gary H. Duncan from Talbot, J. D.,
et. al., Science 251: 1355, 1991) shows activation of the cerebral cortex
by a hot probe (which the subjects describe as painful) applied to the
forearm (which forearm?).

Most cancers consume large amounts of glucose (cellular respiration is less efficient than in
normal cells so they must rely more on the inefficient process of glycolysis). Therefore PET
scanning with 18F-fluorodeoxyglucose is commonly used to monitor both the primary tumor and
any metastases.
 3. MRI = Magnetic Resonance Imaging

This imaging technique uses powerful magnets to detect magnetic molecules within the body.
These can be endogenous molecules or magnetic substances injected into a vein.

fMRI = Functional Magnetic Resonance Imaging

fMRI exploits the changes in the magnetic properties of hemoglobin as it carries oxygen.
Activation of a part of the brain increases oxygen levels there increasing the ratio of
oxyhemoglobin to deoxyhemoglobin.

The probable mechanism:

• The increased demand for neurotransmitters must be met by increased production of ATP.
• Although this consumes oxygen (needed for cellular respiration),
• it also increases the blood flow to the area.
• So there is an increase — not a decrease — in the oxygen supply to the region, which
provides the signal detected by fMRI.

4. Magnetoencephalography (MEG)

MEG detects the tiny magnetic fields created as individual neurons "fire" within the brain. It can
pinpoint the active region with a millimeter, and can follow the movement of brain activity as it
travels from region to region within the brain.

MEG is noninvasive requiring only that the subject's head lie within a helmet containing the
magnetic sensors.