Medical Neuroscience explores the functional organization and neurophysiology of the human central nervous system, while providing a neurobiological framework for understanding human behavior. In this course, you will discover the organization of the neural systems in the brain and spinal cord that mediate sensation, motivate bodily action, and integrate sensorimotor signals with memory, emotion and related faculties of cognition. The overall goal of this course is to provide the foundation for understanding the impairments of sensation, action and cognition that accompany injury, disease or dysfunction in the central nervous system. The course will build upon knowledge acquired through prior studies of cell and molecular biology, general physiology and human anatomy, as we focus primarily on the central nervous system. This online course is designed to include all of the core concepts in neurophysiology and clinical neuroanatomy that would be presented in most first-year neuroscience courses in schools of medicine. However, there are some topics (e.g., biological psychiatry) and several learning experiences (e.g., hands-on brain dissection) that we provide in the corresponding course offered in the Duke University School of Medicine on campus that we are not attempting to reproduce in Medical Neuroscience online. Nevertheless, our aim is to faithfully present in scope and rigor a medical school caliber course experience. This course comprises six units of content organized into 12 weeks, with an additional week for a comprehensive final exam: - Unit 1 Neuroanatomy (weeks 1-2). This unit covers the surface anatomy of the human brain, its internal structure, and the overall organization of sensory and motor systems in the brainstem and spinal cord. - Unit 2 Neural signaling (weeks 3-4). This unit addresses the fundamental mechanisms of neuronal excitability, signal generation and propagation, synaptic transmission, post synaptic mechanisms of signal integration, and neural plasticity. - Unit 3 Sensory systems (weeks 5-7). Here, you will learn the overall organization and function of the sensory systems that contribute to our sense of self relative to the world around us: somatic sensory systems, proprioception, vision, audition, and balance senses. - Unit 4 Motor systems (weeks 8-9). In this unit, we will examine the organization and function of the brain and spinal mechanisms that govern bodily movement. - Unit 5 Brain Development (week 10). Next, we turn our attention to the neurobiological mechanisms for building the nervous system in embryonic development and in early postnatal life; we will also consider how the brain changes across the lifespan. - Unit 6 Cognition (weeks 11-12). The course concludes with a survey of the association systems of the cerebral hemispheres, with an emphasis on cortical networks that integrate perception, memory and emotion in organizing behavior and planning for the future; we will also consider brain systems for maintaining homeostasis and regulating brain state.
Neurobiology of Emotion, part 4
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Medical Neuroscience
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Complex Brain Functions: Sleep, Emotion and Addiction
In this concluding module of Medical Neuroscience, we will consider the neurobiology of sleep and the neurobiology of emotion, including addiction. Both topics involve explorations of complex, widely distributed systems in the forebrain and brainstem that modulate states of body and brain.
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Leonard E. White, Ph.D.Associate Professor
Department of Neurology, Department of Neurobiology, Duke University School of Medicine; Department of Psychology & Neuroscience, Trinity College of Arts & Sciences; Director of Education, Duke Institute for Brain Sciences; Duke University
So let's turn our attention now from the amygdala here in the anterior and medial
part of the temporal lobe, to the orbital and medial part of the prefrontal cortex.
So I'll just remind you again by showing you in this brain model.
The orbital cortex is the ventral portion of the frontal lobe, that sits just above
the orbits of the eyes. And it continues on to the medial surface
of the hemisphere, where we find just above this orbital cortex.
This medial prefrontal sector involving the medial portion of the superior
frontal gyrus, as well as the anterior part of the cingulate gyrus.
And these areas continue, and reach a interesting region called the subcallosal
area right below the genu of the corpus callosum.
So we've learned quite a bit about the functions of the orbital and medial part
of the prefrontal cortex from studying their anatomical connections.
We know that this part of the prefrontal cortex receives inputs from the amygdala
I've already described for you. It's also receiving inputs from virtually
all the other sensory systems. And it's also receiving input from the
associational cortical area. Especially, the associational cortex of
the parietal lobe and temporal lobe. We think that this cortex is involved in
emotional learning, I'll say much more about that in just a few minutes, as well
as in the interpretation of social cues. This cortex is involved in planning
appropriate social behavior. The formation of advantageous real-life
decisions. We might consider this to be a
contribution to our faculties that are involved in reason, and rational decision
making. So, just in a little bit more detail now,
the orbital medial prefrontal cortex is involved in emotional processing.
And it does so in a way that allows our emotions to provide a source of input
that will help us to interpret social cues.
And, as a consequence, it will assist us in planning appropriate behavioral
responses as we engage in social interactions.
Now, the role that this portion of the prefrontal cortex plays in emotion, bears
much similarity to the role that we ascribe to the amygdala.
It's involved in emotional learning, but especially when the rewards are in the
form of factory signals and gustatory signals.
That is, in the form of sense and in the form of food rewards, but it's much more
than that. The orbital and medial prefrontal cortex
is involved in the ongoing analysis and modification of behaviors.
Especially when the reinforcement contingencies are rapidly changing.
We consider this a form of emotional relearning.
Imagine just the complexity of being let's say in mixed company.
And a social situation be it at a club, or at a party, or just engaged with a
group of friends, and perhaps some new acquaintances.
there are many complex dynamics that work here.
And sometimes the kind of conversational devices that work in one interaction with
one kind of person, may have a very different meaning with a different type
of person. Perhaps a person just of a different
background, maybe a different gender. but the point is that these social
situations are highly dynamic and require a great amount of agility.
And it's that social agility, that is a particular challenge to this orbital
medial sector of the prefrontal cortex. And the role that it plays in
interpreting these kinds of complex social cues to guide appropriate
behavior. We think that this sector of the
prefrontal cortex is necessary for the assessment of future consequences.
And the implementation of advantageous decisions.
And I'll have more to say about that in just a few minutes.
Now, let's consider what might happen with injury to this part of the brain.
And, much of what we've learned about such cases, stems from studies of that
famous case of Phineas Gage back in the 19th century.
Who had this iron rod blown through the anterior part of his cranium, with severe
damage to his orbital and medial prefrontal cortex.
Well, in the decades since the life and times of Phineas Gage, other patients
have been identified. And now there is a cohort of patients
that are being followed. Who have had damage from either the
growth of tumors or neurosurgical resections or strokes, or traumatic brain
injuries. That have shed considerable light onto
the contributions of this part of the brain to human cognition and social
behavior. So, what we've learned is that people
with injury to this part of the brain show, typically, no impairments in
sensory function and, and volitional motor control.
Except for impairments in the olfactory sense and in the gustatory sense.
And together, those combine to give us a sense of flavor.
So, so these dimension of the chemical senses are impacted with damage to this
part of the brain. But otherwise the rest of our sensory
systems are intact and for the most part are volitional motor system is intact.
Again, with our standard means for doing neuropsychological assessments, these
patients seem to be doing perfectly fine. Yet there are real impairments in
emotional experience and expression. And perhaps as a consequence, there are
impairments in the capacity of these individuals to make rational decisions.
Especially when these decisions pertain to the domain of personal and social
affairs. One very curious feature of this
impairment in decision making is that, these patients tend to have a
pathological inability to make advantageous decisions when it comes to
real life situations. as we see it's not just that they behave
at chance. It's that they actually tend to make poor
decisions that can have serious consequences for their real life
circumstances. Now much of the leading work that has
gone on in the study of patients with damage to this part of the brain are in
fact the same group that has brought to the attention of patient SM.
A group in Iowa that has studied these patients with brain injuries.
And this group, quite presciently recognized that the standard battery of
neuropsychological assessments. Really did not seem to be sufficient to
get at the true nature of the real life deficits in these patients.
So they proposed a new kind of test that they called the Iowa gambling test.
So this test involved a set of playing cards that could be divided into, four
decks and the patient is instructed to draw a card from one of these decks.
What the patient doesn't know is that there is a certain protocol for providing
financial reward or financial penalty from drawing a card from one of these
four decks. And the way this is set up is that this
patient's given a certain allotment of money at the beginning of the experiment.
And the patient begins to choose from these decks of cards.
And two of these decks of cards we might call disadvantageous.
Because while there may be large gains, there are more frequent moderate losses
or infrequent large losses. And the aggregate result of drawing cards
from these particular decks over the course of this experiment, is if there
will be net financial losses. If these patients choose from decks A or
B. However, if the patients are drawing
cards from decks C or D, there may be small monetary gains, but the losses are
either going to be small themselves. Or they'll be much more infrequent and of
a more moderate dimension. So this is a more conservative strategy,
that leads to net financial gain. And over the outcome of the experiment,
we might consider this to be advantageous decision making strategy.
So what we find in normal subjects, over the course of time is that most of us
very quickly begin to explore the disadvantageous decks.
And over time, we choose less and less from the disadvantageous decks and more
and more from the advantageous decks. So we end up with a net financial
benefit, that is we, we end up making a little bit of a profit.
As we explore the roles that govern the financial gains and losses in this game.
Now, interestingly, what patients with damage to their orbital medial prefrontal
cortex do, and also patients with amygdala damage.
They tend to chose preferentially from this disadvantageous deck, and it never
quite seems to go away. They will choose from the advantageous
decks as they begin to figure out that that might be a useful strategy.
But they never quite seem to do so with greater prevalence, over choosing from
the decks that lead to the financial loss.
It's as if what they are drawn to is the impulsive prediction of significant
reward, even though over time that strategy will lead to a net financial
loss. And this paradigm in what is called this
Iowa gambling task is, getting a little bit closer to the real-life impairments
that these patients experience. As they make decisions in the real world,
many of them financial decisions. So, perhaps not surprisingly, many of
these patients end up going bankrupt, because they terribly mismanage their
resources. They also suffer from broken human
relations within their family, and within their extended circle of friends.
Again because their decisions are based mainly on assessments of short term gain.
They seem to fail in the proposition of projecting out long term consequences of
their action. And that's where the connection between
emotion and reason seems to come into play.
Now, the lead investigator that has developed this line of thinking is
Antonio Damasio. but many others of his colleagues have
contributed over the years to the study of these patients and to the formulation
of the ideas. And I for one am quite compelled by these
ideas, and think that Dr Damasio and his team might actually be on to something
quite important. So Damasio and colleagues have proposed
what they call the somatic marker hypothesis of reason.
And as you'll see, this is very much a, a Neo-Jamesian idea reflecting William
James and Lange's theory of emotion. So at the heart of this idea is the
notion that rational decision making entails a set of covert evaluations of
future consequences. Now these covert evaluations take the
form of what Damasio calls mental images. And these mental images represent the
possible outcomes of our decisions that might trigger states of body and brain.
And Damasio calls these somatic states. So these are somatic states that would
mark these mental images with emotional valence.
Now what he's getting at is that the brain might actually be representing the
state of the body, as it experiences the consequences of our decisions.
And that these brain representations of somatic state, then become a source of
bias that can influence the outcome of these covert deliberations.
Now these somatic states may be truly somatic, and this would be very much a
James-Lange proposition. This would involve the activity of
autonomic and skeleto-muscular effector systems.
But, as Damasio has argued, these somatic states might be vicarious.
And what he means by that is that they may only involve the brain constructs,
the neural representations of this visceral motor, and somatic motor
activity. We imagine that this would be focus in
our parietal and our insular regions of the cerebral cortex.
And here's where there's a bit of a departure with the classical, a,
James-Lange theory. Damasio would propose that, indeed, the
relationship between body and brain may not be obligatory for the operation of
these mental images. Rather, in the parietal and the insular
cortices, there may be a stored memory of body state that can be mobilized.
And used to mark that mental image with an emotional valiance that reflects the
way the body feels when experiencing one possible emotional outcome or another.
So in Damasio's conception of decision making, these somatic markers are biasing
the covert deliberations towards the implementation of advantageous decisions.
And this helps us understand what might happen with damage to these parts of the
brain. Where this important somatic marker
function is disabled. As a consequence, without being able to
bias our decision making toward future advantage, what we're left with is the
allure of short-term gain. And we tend to act more impulsively,
without these somatic states biasing or decision making in our future
orientation. Well, I'd like to conclude our tutorial
by talking about this much more delusive aspect of the neurobiology of emotion.
That is, the subjective feelings that are associated with our emotions.
So where do these feelings come from? And why should they exist in the first
place? As I suggested earlier, having an
appropriate fear response need not actually make you feel afraid.
But yet it does. So this has led to the proposition that
perhaps feelings are the consequence of having emotions within a cognitive
faculty. That is capable of self reflection, of
introspection, of working memory. So the notion here is that perhaps
feelings are kind of emotional working memory.
So imagine then, that there are the appropriate stimuli that might trigger
the experience of an emotion as we've been discussing.
The stimuli will impact our amygdala dependent associative learning systems.
As well as those associative learning networks in the orbital and medial
prefrontal cortex. Of course, we will also generate explicit
representation of these events, through our hippocampal dependent memory systems.
And together, the implicit and the explicit will interact in interesting
ways between amygdala systems and hippocampal systems.
But, also, they will influence our prefrontal networks.
And, it's there in the prefrontal cortex that we will have an immediate conscious
experience of our emotional feelings. So you'll recall that when we talked
about working memory in the dorsal lateral portion of the prefrontal cortex.
We describe the activity of neurons that are maintaining representation of the
goal that is motivating our behavior. Well we think that something like that
might be going on in the orbital and the medial sectors of the prefrontal cortex.
Where the object of implicit representation is being sustained in the
activity patterns of this part of the brain.
And from that perspective, perhaps the feeling associated with the emotion is a
reflection of a kind of working memory. What we may be doing is maintaining in
our immediate conscious experience the implicit processing, that is motivating
and guiding emotional behavior. So it's really this capacity for working
memory, or there is this capacity for introspection, that is giving us the
feeling of the emotion. [SOUND].
Now, perhaps you are wondering whether non-humans experience emotions in the
same way that we do. well if you're curious about that, you
might start with a fabulous monograph written by non other than Charles Darwin.
And this has become one of the seminal works regarding the expression of
emotion, in not only humans but in non-human animals as well.
I think it's fair enough to state that the capacity for emotion is associated
with the development of this orbital and medial portion of the prefrontal cortex.
With this capacity for an emotional working memory, being critical for the
experience of emotion with the feelings that attend these states of body and
brain. Now when we survey the anatomy of our own
orbital and medial prefrontal cortex Obviously we're impressed with the
development of these regions of the human brain.
And it's tempting to therefore conclude that there must be some dimensions of
emotional experience that are uniquely human.
Well I don't think we, we know that for certain.
But nevertheless, there is no missing the conclusion, that our emotional experience
is a well-developed capacity. That is attributable to the development
of this portion of the human brain. And the ability to experience and to
express emotion is critical for social cognition and healthy human relations.
Well, let's conclude this tutorial by leaving you with a few points of summary.
So what I've tried to describe for you, is that human emotion entails a wide
range of brain and body states. That are characterized by expressive,
somatic motor and visceral motor behaviors, by stereotypical physiological
responses of the body. And by distinct subjective experiences.
These dynamic states of body and brain are likely to arise as a result of an
associative learning process, that attaches emotional valence to sensory
stimuli. Associative emotional learning involves
two key centers in the forebrain, the amygdala in the anterior medial temporal
lobe. And the orbital and medial sector of the
prefrontal cortex. The amygdala is a primary neural center
for associative learning. And one important contribution of the
amygdala is to process those signals that will increase our vigilance.
Because they predict the presence of risk or threat.
Another important neural center, of course, is the orbital and medial sector
or the prefrontal cortex. This also contributes to emotional
learning, especially when the contingencies of reinforcement are
rapidly changing. And this is certainly one way to
understand the complex dynamics of real-life, real-world social engagement.
Well, I hope you've become as fascinated as I have In these parts of the human
brain. And we are just now entering what I
believe will be a great new era of discovery.
Where the mysteries of this orbital and medial sector of the prefrontal cortex,
and its contributions to cognition, will be much better understood.
And as a consequence I think we will have much more insight into who we are as
human beings.
