Physiology

Nervous System

TSU
Faculty of Medicine
2022
Lecture 3
outline

Chapter 8 The Central Nervous System

8.2 Cerebrum
 Cerebral Lateralization
 Language
 Limbic System and Emotion
 Memory
 Emotion and Memory
Cerebral Lateralization

Because of decussation ( crossing

over) of fibers each cerebral cortex
controls movements of the
contralateral (opposite) side of the
body and somatesthetic sensation
from each side of the body projects
to the contralateral postcentral
gyrus.
Each cerebral hemisphere, however,
receives information from both
sides of the body because the two
hemispheres communicate with
each other via the corpus
callosum.
Cerebral Lateralization

The term cerebral lateralization means the tendency for

each hemisphere of the brain to specialize in different
functions.
Each hemisphere is good at certain categories of tasks and
poor at others.

Whereas the two hemispheres have complementary

functions, now the term cerebral lateralization, or
specialization of function in one hemisphere or the other,
is thus preferred to the term cerebral dominance.

The concept of cerebral dominance - analogous to the

concept of handedness.
 Cerebral locations of specific functions

Left Right
hemisphere - hemisphere -
can describe has limited
facial verbal ability; is
appearances most adept at
better than right visuospatial
hemisphere; is tasks; can
better for recognize faces
language and better than the
analytical ability left; ability to
compose music,
but not to
critically
understand it.
Cerebral Lateralization
 Language
Aphasias - speech and language disorders caused by
damage to the brain through head injury or stroke.

The language areas of the brain are primarily located in

the left hemisphere of the cerebral cortex.

Even in the nineteenth century, two areas of the cortex -

Broca’s area and Wernicke’s area - were recognized
as areas of particular importance in the production of
aphasias.
Language
Paul Broca (French) in 1864
found that damage to the
left inferior frontal gyrus
and surrounding areas
resulted in loss of speech
(Broca’s aphasia).

Karl Wernicke (German) in

1874 found that damage
to the superior temporal
gyrus of the left
hemisphere resulted in
loss of speech (wernicke’s
aphasia).
 Language
People with Broca’s aphasia are
reluctant to speak, and when they
try, their speech is slow and poorly
articulated. However, their
comprehension of speech is
unimpaired. They can understand
a sentence but have difficulty
repeating it.
Wernicke’s aphasia is characterized
by speech that is rapid and fluid
but without meaning (“word
salad”). Language comprehension
is destroyed; people with
Wernicke’s aphasia cannot
understand either spoken or
written language.
Brain areas involved in the control of speech
Language
To speak intelligibly, the concept of words originating in
Wernicke’s area must be communicated to Broca’s area;
this is accomplished by a fiber tract called the arcuate
fasciculus.
Damage to the arcuate fasciculus produces conduction
aphasia.
The angular gyrus, located at the junction of the parietal,
temporal, and occipital lobes, is believed to be a center
for the integration of auditory, visual, and somatesthetic
information.
Damage to the angular gyrus produces aphasias, which
suggests that this area projects to Wernicke’s area.
Language
Limbic System and Emotion
The parts of the brain that appear to be of paramount importance
in the neural basis of emotional states are the hypothalamus
(in the diencephalon) and the limbic system.

Limbic system consists of a group of forebrain nuclei and fiber

tracts that form a ring around the brain stem (limbus = ring).

Components of the limbic system are:

 Cingulate gyrus (part of the cerebral cortex)
 Amygdaloid nucleus (or amygdala)
 Hippocampus (“seahorse”)
 Septal nuclei
 Anterior insula
The limbic system
The limbic system
Papez circuit
There is a closed circuit of information flow between the
limbic system and the thalamus and hypothalamus
called the Papez circuit.

James Papez (1883-1958) - an

American neuroanatomist

In 1937 he described the Papez

circuit which is a neural pathway
in the brain thought to be
involved in the cortical control of
emotion.
Limbic System and Papez Circuit
 Papez Circuit
Mammillothalamic
Fornix
tract
Mammillary bodies
of hypothalamus;
Septal nuclei

Hippocampus Anterior Thalamic

Neocortex nuclear group

Parahippocampal Gyrus Cortex of Cingulate Gyrus

 Functions of limbic system
The hypothalamus and limbic system are involved in the
following feelings and behaviors:
1. Aggression (Stimulation of certain areas of the amygdala and
particular areas of the hypothalamus produces rage and
aggression).
2. Fear (By electrical stimulation of amygdala and hypothalamus can
be produced fear; removal of the limbic system can result in an
absence of fear. Humans with damage to their amygdala have
demonstrated an impaired ability to recognize facial expressions of
fear and anger.)
3. Feeding (The hypothalamus contains both a feeding center and a
satiety center. Electrical stimulation of feeding center causes
overeating, and stimulation of the satiety center will stop feeding
behavior in experimental animals).
 Functions of limbic system
4. Sex (The hypothalamus and limbic system are involved in the
regulation of the sexual drive and sexual behavior. The cerebral
cortex, however, is also critically important for sex drive.).
5. Goal-directed behavior (reward and punishment
system) (particular sites between the frontal cortex and the
hypothalamus are responsible for rewarding and punishment. After
electrical stimulation of this areas humans reported feeling of
relaxation and relief.).
Memory

Learning - Acquisition of new information.

Memory - Retention of learned information.

There are many different types of memory.

Specific cortical and non-cortical areas process different

types of memory, or different aspects of memory.
Memory
1. Encoding gone
2. Storage Long Term
Memory
3. Retrieval All the rest

Sensory Retrieval
External Registers
Stimuli

At
ten
tio
n

Short Term
Memory
Memory

The conversion of a short-term memory into a more

stable long-term memory is called memory
consolidation.
Memory

There are different categories of memory:

 short-term memory
 long-term memory

Long-term memory is generally divided into two broad

categories:
 Declarative memory (explicit)
 semantic (fact)
 episodic (event) memory
 Nondeclarative memory (implicit)
Memory
Implicit or Non-Declarative Memory

 Memory for skills, habits and behaviors

 Operates without conscious awareness once learned
 Requires repetition and practice
 Less likely to be forgotten once learned
 Allows many types of behavior to be on “auto-pilot”

Procedural memory refers to the knowledge of how to do

something.
Memory
Explicit or Declarative Memory

Declarative memory is memory that can be verbalized;

 Memory of “facts” or “events”;

 Can be consciously recalled;
 Easy to acquire, easy to forget;
Memory
Brain Regions in Memory

Clinical studies of amnesia (loss of memory) suggest that

several different brain regions are involved in memory
storage and retrieval.
Many different brain areas play a role in different types of
memories.

People with amnesia have impaired declarative memory.

Memory
Brain Regions in Memory

The consolidation of short-term into long-term declarative

memory is a function of the medial temporal lobe.

Medial temporal lobe structures

that are critical for long-term
memory include:
 the hippocampus,
 the surrounding hippocampal
region of parahippocampal
and entorhinal cortex,
 amygdale.
Memory
Brain Regions in Memory
It should be remember the hippocampus is no longer needed
once the memory has become consolidated into a more
stable, long-term form.

An amnesiac patient known as “E.P.” with bilateral damage

to his medial temporal lobes, for example, was able to
remember well the neighborhood he left 50 years before
but had no knowledge of his current neighborhood.

This type of amnesia is Anterograde Amnesia.

Memory
Brain Regions in Memory

 Lesions of the left medial temporal lobe impairs verbal

memory.
 Lesions of the right medial temporal lobe impairs
nonverbal memories, such as the ability to remember
faces.
 The amygdala appears to be particularly important in the
memory of fear responses.
 Inferior temporal lobes are sites for the storage of long-
term visual memories.
 Left inferior frontal lobe has shown to participate in
performing exact mathematical calculations because it
stores verbally coded facts about numbers.
Memory
Brain Regions in Memory

Surgical removal of the right and left medial temporal lobes was
performed in one patient, designated “H.M.” in an effort to treat
his epilepsy.
After the surgery he was unable to consolidate any short-term
memory. He could repeat a phone number and carry out a
normal conversation; he could not remember the phone number
if momentarily distracted, however, and if the person to whom
he was talking left the room and came back a few minutes later,
H.M. would have no recollection of having seen that person or
of having had a conversation with that person before.
H.M.’s deficit was in declarative memory.
His nondeclarative memory - perceptual and motor skills, such
as how to drive a car - were still intact.
Memory
Brain Regions in Memory

Prefrontal cortex (the most anterior portion of

the frontal lobes) is involved in
 short-term memory (as for a phone number
that must be kept in mind to dial but then
quickly forgotten),
 planning (remembering to perform
sequential actions), and
 the inhibition of inappropriate actions (such
as answering a stranger’s ringing
telephone).
There is evidence that signals are sent from
the prefrontal cortex to the inferior temporal
lobes, where visual long-term memories are
stored.
Memory
Brain Regions in Memory

Particular aspects of the memory - visual, auditory, olfactory,

spatial, and so on - are stored in particular brain areas, and the
cooperation of all of these areas is required to elicit the
complete memory.
As an example of the diffuse location of memories, working
memory - the ability to keep information consciously for a short
time - is stored differently depending on whether it involves
keeping several numbers until typing them, or whether it
involves spatial information, such as backtracking to pick up an
item skipped while browsing in a new store.

However, both types of working memory require the prefrontal

cortex.
Memory
Brain Regions in Memory
Alzheimer’s Disease

People with Alzheimer’s disease have:

1. loss of brain weight and volume, a decreased cortical
thickness that correlates with cognitive decline
2. losses of specific neuronal populations (as in the
hippocampus and cerebral cortex), of dendritic spines
and synapses, and of neural network function
3. an accumulation of extracellular protein deposits
called amyloid senile plaques
4. intracellular protein deposits forming neurofibrillary
tangles.
Alzheimer’s Disease
In Alzheimer’s disease, an amyloid precursor protein (APP)
may be broken down by β -secretase and then ɣ -
secretase into peptides called amyloid beta (Aβ).

The Aβ peptides can associate into dimers and oligomers,

and then grow into fibers in the form of β -pleated sheets
that compose the amyloid senile plaques.

It is the soluble dimers and oligomers of the 42-amino-acid-

longform of Aβ , more than the plaques, that promote
Alzheimer’s disease
Alzheimer’s Disease

Alzheimer’s disease may depend on another protein,called

tau.
Normal tau proteins bind to and stabilize microtubules in
axons.
In Alzheimer’s disease they become excessively
phosphorylated and redistributed to the neuron cell body
and dendrites.
There they aggregate together and become insoluble,
forming the neurofibrillary tangles.
Not the neurofibrillary tangles, but rather the more soluble
intermediate forms of tau may produce the toxic effects.
Alzheimer’s Disease

Drugs for treating Alzheimer’s disease:

1. Inhibitors of acetylcholinesterase
2. An antagonist of glutamate
3. Drugs for treating depression
Memory
Synaptic Changes in Memory

Short-term memory may involve the establishment of

recurrent (or reverberating ) circuits of neuronal
activity. This is where neurons synapse with each other
to form a circular path, so that the last neuron to be
activated then stimulates the first neuron.

Model for a reverberating circuit.

Source:https://doi.org/10.5540/tema.2020.021.03.0601
Memory
Synaptic Changes in Memory

Long-term potentiation (LTP) is a type of synaptic

learning, in that synapses that are first stimulated at high
frequency will subsequently exhibit increased excitability.
Memory
Synaptic Changes in Memory

Some proposed mechanisms responsible for long-term potentiation (LTP).

The neurotransmitter glutamate can bind to two different receptors - AMPA and NMDA.
The activation of the NMDA receptors promotes an increased concentration of
Ca2+ in the cytoplasm, which is needed in order for LTP to be induced. LTP is believed to
be a mechanism of learning at the level of the single synapse. (CaMKII =
calcium/calmodulindependent protein kinase II).
Memory
Synaptic Changes in Memory

Dendritic spines Pyramidal neuron

with dendritic
spines
Memory
Neural Stem Cells in Learning and Memory
Neurogenesis (the formation of new neurons) has been
shown in mice to be promoted by physical exercise and
by an enriched environment. By contrast, aging and
stress have been shown to reduce neurogenesis.
Neurogenesis in the hippocampus accompanies the
learning of particular tasks, such as the ability of mice to
learn a water maze.

Significant rate of neurogenesis in the adult human

hippocampus suggests that it may likewise play a role
in human brain function.
Emotion and Memory
Limbic System

Emotions influence memory, in some cases by

strengthening, and in others by hindering, memory
formation.

The amygdala is involved in the improvement of memory

when the memory has an emotional content.

The patients who have damage to both amygdaloid nuclei

lose the usual enhancement of memory by emotion.
Emotion and Memory
Limbic System

Although strong emotions enhance memory encoding

within the amygdala, stress can impair memory
consolidation by the hippocampus and the cognitive
functions and working memory performed by the
prefrontal cortex.

As a result, stress can promote the storage of

emotionally strong memories but hinder the retrieval
of those memories and working memory.
 Emotion and Memory
Prefrontal Cortex

The prefrontal cortex is involved in higher cognitive

functions, including memory, planning, and judgment.
The prefrontal cortex is also required for normal
motivation and interpersonal skills and social behavior.

The two parts of prefrontal cortex - the lateral prefrontal

area and the orbitofacial prefrontal area have
different functions.
 Emotion and Memory
Prefrontal Cortex

1) orbitofacial area of prefrontal cortex

2) lateral prefrontal cortex

The orbitofrontal area of the prefrontal cortex confers the ability to consciously
experience pleasure and reward. Connections between the orbitofrontal cortex,
the amygdala, and the cingulate gyrus are very important for the emotional
reward of goal-directed behavior.
People with damage to the lateral prefrontal area of the precentral cortex show a
lack of motivation and sexual desire, and they have deficient cognitive functions.
People with damage to the orbitofrontal area of the prefrontal cortex, in contrast,
have their memory and cognitive functions largely spared but experience severe
impulsive behavior, verging on the sociopathic.
Emotion and Memory
Prefrontal Cortex
One famous example of damage to the orbitofrontal area of the
prefrontal cortex was the first case to be described, in 1848 – a case of
Phineas P. Gage.
Emotion and Memory
Prefrontal Cortex

A 25-year-old railroad foreman named

Phineas P. Gage was tamping blasting
powder into a hole in a rock with a metal
rod, when the blasting powder exploded.
The rod – 120 cm long and 3cm thick - was
driven through his left eye and brain, and
emerged through the top of his Skull.
After a few minutes of convulsions, Gage
got up, rode a horse into town, and walked
up a long flight of stairs to see a doctor.
He recovered well, with no noticeable
sensory or motor deficits. His associates,
however, noted striking personality
changes.
Reading material
Stuart Ira Fox (2016). Human
Physiology, 14th edition

Chapter 8, pp. 216 - 225