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Neurophysiology for Medicine
Association Areas and Memory
The 5 main functional
subdivisions of the cerebral
1) Primary sensory. Occipital
The primary sensory areas is where the
sensory information first enters the
2) Higher order (secondary)
Higher order visual, somatosensory, and Primary
auditory lie near the respective primary sensory taste
area. This is where sensory information and motor
is further processed. visual
3) Association areas. auditory
a) Prefrontal, and b)
Parietal-Temporal-Occipital areas. Higher order
This is where: i) different modalities Premotor somatosensory
combine. ii) attention is shifted iii) Higher
planning occurs and iv) memories are order senory Higher order
stored. In humans they occupy about and premotor visual
80% of the cortex.
Premotor areas are higher order motor
areas that send commands to the
primary motor areas. Higher order
5) Primary motor. auditory
The primary motor areas send Association
commands to the muscles. In the rat, Prefrontal
primary sensory and motor areas association
occupy nearly all the cortex.
Reference to Neuroscience Purves et al 4th Edition
1 revised 12-01-2010
What is the general pattern of connections between primary,
secondary, and association areas?
Higher order Association
motor Premotor Prefrontal
Long loop reflexes
Short loop reflexes
sensory Sensory attention
long term memory
Short loop reflexes mediate rapid, but simple, responses eg swatting a mosquito.
Long loop reflexes, eg writing down the name of a seen object, require the complex processing
power of the association regions.
Gray and White Matter Neuron
Each neuron’s axons, which form the white Cell Body Gray
matter of the cortex, make connections with Matter
1000’s of other neurons in the gray matter.
These extensive interconnections predispose White
the cortex to epilepsy. A locus of abnormal Matter
activity in one area quickly spreads to other Axon
regions leading to a seizure. These
interconnections are, as we will see later, where
our memory is.
b) At the cellular level, which are the input and output layers? P668
Information arrives in layer 4, spreads to Columns 200-500um F26.3
more superficial and deeper layers, and
is finally integrated by output cells whose primary sensory primary motor
bodies are located in layers 3 and 5. I
Layer 4 receives input from the thalamus and 2
other cortical regions. It is thickest in primary
sensory regions. The striate cortex (primary
visual) is so called because of its thick layer
Layers 3 and 5 send output to other cortical
and sub cortical regions. These layers are output to other
thickest in primary motor cortex. Such cortical regions
input and sub-cortical
anatomical differences allow Brodman to
structures such as
divide the cortex into more than 50 areas. the thalamus and spinal cord
Only now are we confirming that Beach has a
unique function. All have columns.
c) List the main functions of each association area and the
experimental supporting evidence.
Planning and working memory
The prefrontal cortex has become larger, as a percentage of total brain size, over the course of
evolution. Close your eyes, wait, and then point to a particular object that you remember being
in the room. Your ability to remember the location of an object is an example of spatial working
memory, a form of short term memory. Lesions in the prefrontal association cortex produce
deficits in motor tasks that are spatial and delayed. Children prior to the age of 1 yr have not
developed this working memory. If a toy is covered by one of two covers, the child cannot find
it. Out of sight is out of mind.
These are large areas located on the underside of the cortex. There are two parts.
1) Orbito frontal: involved in emotion. After lesions, no anger is displayed when the patient
makes mistakes. Because this has a calming effect, frontal lobotomies used to be a popular cure
for aggression. Unfortunately it also destroyed initiative. Neurologist António Egas Moniz won
the Nobel Prize for medicine in 1949 for inventing this technique. Dr. Walter Freeman used an
ice pick hammered through the back of the eye socket into the brain. He performed thousands of
lobotomies in minutes from his office. His patients included Rosemary Kennedy, the sister of
John F. Kennedy.
Parietal- Occipital-Temporal (PTO):
Functions: Box 26B
1) Poli-modal convergence of senses.
Primary sensory areas are activated by a single sensory modality. In the PTO we find areas
activated by more than one modality
The right PTO specializes in the spatial representation of objects by touch, sight, or sound.
The left PTO specializes in language: the sound of words, written words (sight), or Braille
2) Attention. The PTO allows us to focus in on specific objects and neglect others. An
analogy that is simple and useful in beginning to understanding attention is that of a flash light
that selectively casts light on
particular objects. One's capacity to attend to more than one object is limited. The limit is 3 to 5.
3) Inferior Temporal lobe: involved in long term memory. We will look at memory in
detail later in this session.
The converse of attention is neglect.
A lesion of the right PTO causes neglect
of the left half of objects. The patient is
unaware that one half is gone. When a patient
is asked to copy a flower, the patient will draw
only the right side. This is independent of
where the patient is looking.
This is different from the deficit seen after
a right V1 lesion. Here the patient is blind to
everything to the left of where the eyes look.
The neglect patient also neglects the left Normal Right PTO
side of his body. Lesion
You might suppose the a lesion of the left PTO would result in neglect of things on the right.
Strangely it does not. Functional imaging shows this is because the right PTO contains a bilateral
representation (of things on the left and right) while the left contains only a representation of
things on the right.
Thus after a lesion on the left, the right side still attends to things on the right (as well as left).
After a lesion on the right, the representation of things on the left is lost.
Front Front Front
normal left lesion right lesion
How and why do the two sides of the cortex differ in function?
a) In what tasks does each hemisphere excel?
Dominant (usually left) - sequential or serial tasks
eg: language (reading writing speaking signing), analytic (math A=B, B=C,
Non-dominant (usually right)- tasks requiring parallel processing
eg: spatial tasks, intuitive (C resembles O as I resembles L), geometry, music
b) Patients with section of the corpus
A patient with a lesion of the corpus
callosum is shown an apple on the left.
The patient cannot name the apple because
it is not seen by the language center on the
The patient can visually recognize an apple
and pick it out from a group of other Front
objects with his left arm (the one controlled
by the right side of the brain). to left arm
Two independent brains function in one
person (e.g. patient would hug his wife with
one arm and push her away with the other).
Learning & Memory P792
Memory: information that is stored. (The basis of memory is the strength of synapses)
Learning: the storage process. (Learning occurs when the synaptic strength is changed.)
Remembering: the retrieval of stored information.
Types of Memory
Short term / Working memory
l scratch pad which allows for temporary
a sort of
storage of information Long term
l 1: storing numbers when adding.
l 2: spatial location of objects (eg when
you close your eyes and point to remembered
l tonic activity of neurons in the frontal
l limited capacity (limited to about a 9
Has a very
digit new #)
Declarative (knowing that)
Characteristics: Reflexive / Procedural (knowing
l representations of objects and events e.g. the face how)
of a friend or the friend’s telephone # Characteristics:
l associations e.g. name with face
involves l skills such as skiing or how to
l often established in one trial dial a telephone
l of memory
conscious l slowly by practice
l after the age of 2 yrs
starts only l conscious of remembering
one is not
l by amnesia
affected the skill
l formation (learning) requires the
memory l develop at birth
hippocampus in medial temporal lobe l is not affected in amnesia
l storage of places and faces occurs in
memory l much of the CNS, for
inferior temporal areas. example, the tuning of binocular V1
cells during the critical period for
stereopsis & the cerebellum for motor
Declarative memory is divided into two parts.
l Remembering particular objects and l Remembering faces and places.
places in one’s personal past. l Remembering facts and
Episodic memories are composed of concepts, eg that Paris is in
several semantic memories. France.
l Associating who and what with l places are recognized
where and when. in the parahippocampal place
l 1: In episodic memory one
Example area (PPA) in the medial parts of
not only recognizes the person in the the inferior temporal lobe.
picture but also when the picture l faces are recognized in
was taken."My wife and I visited the fusiform face area (FFA) in
Paris when the kids were young". more lateral areas of the inferior
l 2: The sequence of places
Example temporal lobe.
one passes while walking across a
city. The synthesis of such
representations provides us with a
map of the spatial layout of the city.
The amygdala is also involved face recognition.
When we encounter someone we know two
A) the conscious identification of who that
B) an automatic concurrent ‘glow’ of
This ‘glow’ can occur without the conscious
recognition of the person.
This ‘glow’ is accompanied by autonomic
responses such as sweating. These responses
can be entirely unconscious.
These autonomic responses are the basis of lie
detector tests which measure changes in skin stream
conductance caused by sweating.
These two aspects of recognition are mediated
by two parallel pathways fusiform face limbic
A) the inferior temporal cortex (fusiform face area amygdala
B) the amygdala
A lesion of A but not B produces sense of conscious
familiarity without being able to identify who identification
that person is (prosopagnosia).
A lesion of B but not A produces the converse.
The patient can identify who the person is but
has no sense of familiarity.
One young man, after a car accident which
affected the path through the amygdala,
1) could recognize his parents
2) but felt that they had been replaced by aliens
(ie no sense of familiarity)
Mechanisms of Learning
You can be trained to produce blinks
in response to a sound by classical
One begins with a naive subject; one
that does not blink in response to a flash of
light or a sound.
The next thing needed is a good
teacher: a stimulus that will always produce a
A puff of air is a good teacher. A puff
of air, through strong synapses, almost always
produces a blink.
This is called classical conditioning:
the puff depolarises the blink cell. This
strengthens the synapses from the paired
That is, the puff of air teaches sound to
produce a blink.
A similar strengthening and pruning of
synapses is the basis of all forms of long term
After conditioning, the synapse from
the sound is strong and can produce a blink on
That is, the blink becomes associated
to sound but not to some other stimulus such
as a light.
This conditioning also involves
pruning of connections. While connections
from sounds are strengthened, those from
light are weakened.
This procedural type of memory
involves the cerebellum.A lesion of the deep
cerebellar n. eliminates the learnt blink to a
Billions of such connections are
changed in a similar way throughout one's life
in other parts of the brain.
Encoding Long Term Declarative
The ventral stream 1) extracts the visual
features, 2) encodes them as objects, and 3)
stores them temporally in working memory.
Consolidation of short term working memory
into long term declarative memory involves
the hippocampus. Unlike procedural long term
memory which requires repetitive practice,
declarative memory often require only a single
exposure. This is because the hippocampus is
an excellent teacher.
The hippocampus is located in the medial part
of the inferior temporal lobe. It is a unique part
of the cortex. Unlike other cortical areas, it
continuously generates new neurons.
The hippocampus is well connected: an
important attribute of a good teacher. It
receives input from all the association areas
and sends signals back to them as well as
others thus creating new associations. The
hippocampus associates the current features
of the perceived object with other older
memories related to the same object. The
activation somehow binds together/associates
various feature combinations into a rich multi
modal memory. The memory of your
grandmother's face is associated with the
sound of her voice and a multitude of related
memories. This long term memory requires
the changes in the structure of synapses. These Voice
structural changes involve the expression of
genes and the synthesis of proteins. Face
Patients like HM suggest that once this long
term memory is formed, seeing the same
object, e.g grandmother’s face, will activated
the same associations directly, without the
need of activating the hippocampus.
Remembering involves transferring these long
term memories in temporal lobe association
areas back to working memory in the frontal Voice
lobe by as yet a poorly understood process. Face
Brenda Milner's famous patient H.M. P801
Much of what we know about the consolidation of long term stems from Brenda
Milner's work at McGill U. with patient H.M.
To relieve severe epilepsy,perhaps caused by a bicycle accident at the age of nine,
H.M.’s medial part of the temporal lobe and
for as long
(what) e.g. language
as not distracted
old memories new memories
recognizes cannot remember
his mother new acquaintances
old new Anterograde
forgets facts and events forgets facts and
that occurred prior to events that occurred
lesion (as in retrograde anterograde
after the lesion.
Prosopagnosia or damage
H.M. died in 2008 at the age of 82. Remarkably, late in life, he had trouble recognising himself in
a mirror. His memory of himself was as he was at the time of surgery when he was 27. He was
also unable to remember the contribution he made to our understanding of memory.
For practice problems see