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.
Sleep Disorders
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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
Now, here again, we confront the paradox of REM sleep.
So, the thalamocortical neurons are in this depolarized tonic firing mode state
during REM sleep, just as they are during wakefulness.
And this is presumably one reason why there are cogent patterns of activity in
our thalamocortical networks that might be consistent with having a dream, for
example. So while the information is not being
derived from outside of the brain information is being resurrected from
within the circuits that have been modified by previous experience and we
have these hallucination like experiences that, that we call dreams.
Now you may be wondering why it is that sometimes you have really vivid dreams,
and sometimes you might think that you're not dreaming at all.
Well, we've already made the point that we think we all have dreams every night
since we have cycles of REM sleep every night, unless there should be a disorder
of sleep present. And the reason why you may not remember a
dream on any one given night's sleep, may simply be that you didn't wake up while
that dream was happening. If you do find yourself going through a
period in your life where you are recalling many vivid dreams, that's
probably an indication that you're not getting very good sleep, and that you are
waking up repeatedly during these bouts of REM sleep.
so while it's quite normal to remember a dream, I think if you find yourself doing
that more and more frequently then that might be a sign that your sleep is being
more disrupted than it ought to be. Speaking of sleep disorders, let's
conclude our discussion of sleep by considering just a few common disorders
of sleep beginning with, probably the most common one of all, insomnia.
So insomnia refers to impairments associated with the inability to either
fall asleep, to stay asleep, or to experience the normal restoration of
energy and vigor that sleep ought to provide.
So, insomnia, we think, affects about 15% of the population, and it can come from a
variety of sources. One fairly common cause of insomnia is
simply ingesting too much caffeine. So, relative to a control subject that is
showing these nice cycles down through our non REM stages of sleep, back up to
REM. And then back down to stage four or stage
three, sleep through the night. this individual who has consumed an
excessive amount of caffeine is only hitting, slow wave sleep for very brief
periods of time and only in the first couple of hours of sleep.
So notice that the overall duration of sleep in this subject is quite short,
just a few hours, compared to a normal eight or nine hours of sleep.
In a night, and the amount of time that's spent in stage four sleep is far from
normal with this overly caffinated individual.
So again what, what this person has done is they have blocked their adenosine
receptors, which presumably is not activating the ventral lateral preoptic
area sufficiently to counteract the stimulating systems that are otherwise
trying to promote wakefulness. Now, also shown here is benzodiazepine,
which is a form of sleeping pill, and what benzodiazepines do is facilitate
currents that are flowing through those GABA A receptors.
That are being activated by endogenous GABA.
And notice that with the benzodiazepine on board, one reaches stage 4 sleep much
more quickly and then has much more extended periods of this deep stage 4,
slow-wave sleep, compared to control subjects.
So insomnia can be treated in various ways, with pharmaceutical measures or
with various behaviorial measures. But it's one of the most common disorders
of sleep that we have in our population. Another disorder of sleep is when we
misalign ourselves with our circadian rhythms.
So there's a condition called circadian rhythm disorder, and this can happen for
a variety of reasons. There can be physiological causes for
circadian rhythm disorder. there can be lifestyle choices such as
shift work or simply choosing to stay up very late at night, and not get a proper
night's rest on a regular basis. That can result in a drift in one's
circadian alignment to the entrainment that our environment is trying to provide
for us. Well here I am speaking to you at night
with electrical lights illuminating my environment when perhaps I ought to be
drifting off to sleep right about now. So, there are various ways in which we
manipulate our environments and change our lifestyles.
That run the risk of upsetting the alignment that we ought to have with our
environment. Well, another relatively common disorder
of sleep is called sleep apnea. So sleep apnea results in a cessation of
breathing during the sleep. Now, this could be quite a serious
problem, obviously. And so, this typically results from a
mechanical obstruction from the airway. So, people that are somewhat obese are at
risk for this. As our muscle tone begins to relax, as
we're entering our deeper stages of sleep especially if we have some excessive
weight around the region of our neck the region of our pharynx can actually
collapse down upon our airway and occlude the flow of air down into our trachea.
And once that happens then obviously we're not breathing normally and carbon
dioxide builds up very quickly. That can induce a reflexive forced
inspiration of air and that act can be very disruptive.
It can wake us out of sleep and so what we see in this slide here is a record of
someone who is attempting to sleep with sleep apnea.
And we can see that they never enter the deeper stages of sleep at all.
They are simply bouncing around between being awake and being in the lightest
stages of sleep, and having quite a fitful night of it.
So you can imagine why such individuals really struggle so much in their waking
state of fighting off drowsiness and the tendency to actually fall asleep during
times when it would be inappropriate to do so.
Because they're not getting A proper night's rest when they ought to be in a
situation of cycling down into those deeper stages of sleep that this
condition is denying them. So again, thankfully, there are
treatments for sleep apnea. The most common apnea is a positive
pressure system. Which is designed to keep that pharynx
from collapsing down upon the airway during the progression into deeper stages
of sleep. The next sleep disorder I'd like to
mention is called narcolepsy. Now narcolepsy is sometimes called a REM
sleep attack or sleep attack what this is, is a condition that allows for the
intrusion into the waking state of fragments of the state of body and brain
that we normally associate with REM sleep.
So typically people who are having these sleep attacks are not actually asleep.
But they're having elements of REM sleep intrude into their conscious state.
So this can be a terrible condition to have to live with, because the full-blown
experience of REM sleep is seemingly right at the threshold at any moment.
So, for example, one common condition associated with these attacks is
cataplexy. And cataplexy refers to a partial, or
perhaps even a complete paralysis, consistent with the, paralysis of large
skeletal muscles that we see during normal REM sleep.
So imagine these attacks intruding at any moment, during your normal conscious
state, this is what people with narcolepsy have to experience.
And in a rather cruel twist, in the experience of an individual suffering
from this condition, these attacks are often brought on by emotional
experiences, intense emotions, often very intense positive emotions, such as, a
laughter at a pleasant and unexpected experience of some sort.
That might be sufficient to induce one of these attacks.
Now what's going on here, we think, is a mutation in either the gene that produces
this important peptide orexin, or the receptor for this peptide.
one way or another, it seems as though in people who have narcolepsy, there is a
mutation that is affecting the function of the orexin hypocretin system.
And this is going to interfere either with the ability to sustain the awake
state, or it's going to interfere with the regulation of those systems that are
promoting the onset of REM sleep. Now we, we know so much about narcolepsy
because of the discovery of some animal models that like human patients who have
narcolepsy, have mutations in the genes for these critical components of this
orexin system. So thanks to these animal models and the
research that's going on with them, we are beginning to understand much better
how to, approach the intervention and the care of these people that have what
potentially could be a life threatening sleep disorder.
And then lastly, I'd like to just mention restless legs syndrome.
this is a sleep disorder characterized by a feeling in the extremities,
particularly the legs, that movement is necessary in order to relieve a sense of
unease. this might feel like an itch, it could
feel like a tingling sensation. often it's quite hard to describe but
it's a sensation that drives a person to want to move their legs in order to
achieve some measure of relief. Well, restless leg syndrome has been
associated with a deficiency in iron within the dopamine neurons of the
substantia nigra pars compacta. And, and this is suggested that perhaps
there is some deficiency in the dopaminnergic system, presumably
projecting to the putamen, that component of the striatum that is associated with
the loops that govern the movements of the arms and the legs.
So perhaps there is some disorder that is manifest at the level of basal ganglia
circuitry that is providing for this urge or this impulse to move the legs to
achieve some resolution to these feelings.
So. As I think this tutorial has made clear,
sleep is a very complicated business. There are a number of neurochemicals that
are involved in regulating the transitions of states of body and brain.
We're beginning to learn more about them and there are lots of opportunities for
things to go wrong. Either because of disease or disorder or
now, more commonly, because of pharmaceutical agents and dietary factors
that we take into our bodies that interfere with the normal operation of
these systems. So if you are in the health care
professions you should know quite well. How the pharmaceutical agents that you
may be prescribing are interacting with, with your patients are effecting their
sleep cycles, and I hope this tutorial has emphasized for you how critically
important a good night's rest is for promoting health and wellness.
And we need to be all the more vigilant. To protect this important aspect of what
it means to maintain our life on a healthy trajectory when there are so many
opportunities for us to interfere with this process, everything from, a morning
cup of coffee to the lights that illuminate our environments in the night
time. Well, I think I've probably said enough
about that subject, and after all, it is getting on into the evening and I'm
feeling my adenosine rising and my [UNKNOWN] levels lowering so.
I know it's about time for me to turn in. So, I'll see you next time when we will
dive into the limbic forebrain and talk about those brain systems that are
engaged in the experience and the expression of emotion.
So, I'll see you next time, and otherwise I hope we all have a good night's rest.
