Hello, my name is Ralph Lydic. I am a professor of neuroscience at the University of Tennessee. And Burt La Du, professor emeritus at the University of Michigan. I'd like to welcome you to the MOOC entitled Sleep: Neurobiology, Medicine, and Society. The purpose of this segment is to give you an overview of this class, what the material will cover in this first version of Sleep: Neurobiology, Medicine, and Society. I'd like to begin by thanking the number of faculty from five different universities who have contributed content and lectures to this class. These colleagues are all internationally known clinicians and sleep scientists who have worked with us over the past 15 years in developing the actual class at the University of Michigan. The point of this slide from Peretz Lavie's book, entitled Enchanted World of Sleep, is to illustrate the universality of sleep. Sleep applies to all cultures, all people, at all times. And that's seen more dramatically in this NASA image of the world during the night. And you can light in the developed parts of the world, darkness in the less developed parts of the world. And it makes the point that for all 7 billion people on this planet, our ability to perform on a given day is primarily influenced by the quality of our sleep in the previous night. And we'll see as we go through that this quality is also reflected in our autonomic physiology and how our brain functions, as a result of whether we have quality sleep or poor quality sleep. We begin by focusing on the neurobiology of sleep. Sleep, as Bill Dement has said, is of the brain, by the brain, and for the brain. Dr. Helen Baghdoyan, professor at the University of Tennessee, is a neuropharmacologist who has studied he neurochemistry of sleep and wakefulness. The learning points in her talk are to focus, first, on a historical overview of how we understand sleep and how the brain regulates sleep. Beginning with the brain stem and its ability to alter these higher cortical areas of the brain stem, forebrain, and cortical interaction. The brain, of course, is an electrochemical organ. It works and functions by chemical transmission between neurons. And, of course, that's how we treat sleep disorders, largely, by drugs. And Dr. Baghdoyan then describes molecules that regulate various states. Focusing, first, on those that regulate wakefulness and REM sleep because the brain is as excited during rapid eye movement, or REM, sleep as it is during wakefulness. And those neurotransmitters include monoamines, acetylcholine, GABA, Aminobutyric acid or GABA for short, and orexin, also known as hypocretin. During non-REM sleep, or the non-rapid eye movement phase of sleep, we see a predominant role for GABA and adenosine. And Dr. Baghdoyan will describe each of these in relation to the sleep states. And she concludes her lecture by looking at the clinical relevance of these drugs. There is great excitement in neuroscience for understanding better how genes alter behavior. And Dr. Chiara Cirella of the University of Wisconsin will present a lecture on sleep and wakefulness as altered by molecular biology and gene function, and also the ability of behavior to alter gene expression. So the causal area, if you will, points in both directions. We see genes altering sleep behavior, and we see behavior altering gene expression. She emphasizes the genetic modulation of features such as synaptic plasticity, energy metabolism, and the cellular stress response. And she ends her lecture on the genetic basis of sleep by focusing on genes that alter human sleep phenotypes and particular disorders. Now, we say in science that we understand a phenomenon when we can write a mathematical equation describing that phenomenon. That's true in engineering, it's true in biology and it's true in medicine. And Dr. Victoria Booth will present a lecture on math modeling of sleep wake cycles. Dr. Booth is at the University of Michigan in the Department of Mathematics. And she has worked for years to develop mathematical models that describe features of sleep and wakefulness. And she presents learning points that include the aspect of wanting these models to have predictive power, and also the issue of differentiating a story model from a model that is truly quantitative. The image shown on this slide is from Robert McCarley's work over the years presenting the first cellularly based mathematical model of sleep and wakefulness. And that model has now developed and inspired others to go and develop their own models, story models and otherwise, describing sleep and wakefulness. The second third of the course focuses on sleep disorders medicine. One of the things when a person approaches any new material is to try to find the context. Where did this come from? Why don't people know this? How long have they not known this? Humans have existed on this planet, things we would recognize as human, for about 30,000 years. People have been sleeping for a long time. As recently as the 1970s, the first Sleep Disorder Center was founded at Stanford University. And this slide emphasizes that we have a textbook on sleep, a comprehensive textbook on sleep, only as recently as 1989. The National Institutes of Health, whose mandate is to protect and promote health in this country of the United States, developed a National Center for Sleep Disorders Research in 1993. The AMA, or the American Medical Association, as recently as 1996 recognized sleep medicine as an independent specialty. Bill Owen described sleep disorders in medicine as one of the most vibrant new aspects of medicine. In 2001 is when we actually began teaching this class at the University of Michigan. So this was the first comprehensive class at the University of Michigan, began as recently as 2001. And to date, we have about 2,000 sleep centers that are accredited by the American Academy of Sleep Medicine. And these people treat sleep disorders which we'll hear about shortly. And again, in terms of historical context, as recently as 2013, you can see that the 60th anniversary of the discovery of rapid eye movement sleep was observed. So we've been sleeping for a long time. But the study of sleep has been largely phenomenological, and not mechanistic, until very recently. Dr. Ron Chervin provides an overview of sleep disorders medicine. Dr. Chervin directs the Sleep Disorders Medicine Clinic at University of Michigan. And his talk emphasizes the following learning points, both the prevalence of disordered sleep, the broad personal and health impact. By that he means the quality of life and, of course, the things that actually change our physical health. The development over the years of a classification scheme for these disorders. How do we understand them and their relationships to one another? And he begins to conclude his lecture by looking at the clinical approaches, how they differ for different types of sleep disorders. And polysomnographic, or EEG recordings, EMG recordings, used to objectively identify these states, and how that relates to the classification of sleep disorders. With that overview, then, we turn to a very common sleep disorder, obstructive sleep apnea, as presented by Dr. Helena Schotland from the University of Michigan. The learning points in Dr. Schotland's lecture emphasize the relationship between the brain, shown here on the right, the heart, and the lung. And this brain, heart, lung axis many people do not think of as connected. But she makes the point that they are very intimately connected. And it's why, one of the reasons, obstructive sleep apnea is a profound health challenge. She goes through this in wonderful detail, describing the clinical features of obstructive sleep apnea, the risk factors, the pathogenesis. And how specifically this disordered breathing, the closing of the airway repeatedly throughout the night and the inability to move air, how this alters cardiovascular heath. Then she points out treatment, and concludes with a systematic review of studies looking at the efficacy of treatment for sleep-disordered breathing and cardiovascular health. Sleep [COUGH] has long been associated with neuropsychiatric disorders. Dr. Eric Nofzinger, a psychiatrist from the University of Pittsburgh, presents an overview, with the learning points focusing on sleep disruption as a risk factor for the development of psychiatric disorders. We know if a person has a sleep problem that is not attended to, they are at increased risk for developing various types of psychiatric disorders. He then describes the subjective and objective measures of sleep, and how there disturbed differently as a function of different psychiatric disorders. And, finally, he concludes by looking at the significant overlap between brain systems, neurons that control sleep, and the neurobiology of psychiatric disorders. This also emphasizes the point, going back to the earlier section of the course on sleep neurobiology, that for every disease for which we've made progress, it's a disease for which there is an excellent animal model which permits mechanistic studies. And, indeed, all placental, terrestrial mammals exhibit REM and non-REM sleep, as do humans. The next lecture focuses on insomnia. As I said, the most common cause or most commonly presentable sleep disorder. And Dr. Chris Drake of Henry Ford Hospital presents this lecture on causes and consequences of insomnia. Dr. Drake emphasizes the clinical presentation and the nocturnal, diurnal aspects of insomnia. And then describes the theoretical model underlying the treatment modalities for treating different kinds of insomnia and the basic tenants underlying the behavioral treatment of insomnia. He concludes his lecture focusing on pharmacological treatment of insomnia, which leads very nicely into the next lecture, which is provided by Dr. Todd Arnedt from the University of Michigan. Dr. Arnedt's lecture focuses on drug and non-drug options for the treatment of insomnia. And he makes the point that non-drug options, something called CBTI, cognitive behavioral therapy for insomnia, can be as efficacious as drug treatment. He points out that drug treatment works more rapidly. But the non-drug treatments, data suggest, have better long-term outcome. He concludes his lecture by looking at the opportunities for research on non-drug treatment for insomnia. The reason one had interest in this topic is because every drug that has an effect also has a dose dependent, unwanted side effect. This is less problematic and does not exist for non-drug treatments. So this is one of the factors motivating research in behavioral treatment of insomnia. The next section, Sleep and Anesthesia, will be presented by Dr. George Mashour who is at the University of Michigan. Anesthesiologists typically tell their patients they're going to be put to sleep. But they also understand that the state created by anesthesia is not exactly the same as sleep. One of the very interesting questions in this field are what are the similarities and differences between the states of sleep and anesthesia? And how can understanding these similarities and differences help us understand the mechanisms generating sleep and generating anesthesia? I should add that for no anesthetic is it known how the drug makes us unconscious and insensible to pain. And if we knew that, we could develop safer, better drugs with fewer side effects. Dr. Mashour makes this very clear in his lectures. And he talks specifically about the similarities and differences in these states. The phenotypes of sleep and the phenotypes of anesthesia, that means what are the characteristic signs. What evidence is there that they have similar underlying neurobiology or different underlying neurobiology? And he asks the important question, can states of anesthesia satisfy some of the functions of sleep? The class concludes with a brief look at society and sleep's impact on society. And this would be a good point, perhaps, to say there are many aspects of this class that we have not covered during this first version of this MOOC. And I apologize to colleagues and people who are interested in particular areas which are not in this first version. We hope to add them as the class goes on. The societal impacts illustrate the ability, in a highly technical world now, for unwanted performance-related deficits at nuclear power plants, at oil transport facilities, and so on, by a few people, and their ability to impact profoundly society at large. So this is one dramatic aspect of the societal relevance of sleep. The other, of course, are the things that happen every day. What time do we have to wake children who are being bused to school? How do we manage, on a regular daily basis across lifespan, our sleep wake states? And how this impacts society at large. And the first person who sort of addresses these points from a circadian point of view, which refers to the 24 hour rhythms, not the rapid eye movement and non-rapid eye movement rhythms, is Dr. Theresa Lee from the University of Tennessee. The learning points in her lecture are the health impact of sleep. And she talks about the circadian rhythm regulation by the suprachiasmatic nucleus and the hypothalamus. And how light input to this area of the brain directs and regulates non-visually guided behavior. That is, behavior that has to do with the timing of when we feel sleepy, when we feel awake, and so on. These are sometimes referred to as the circadian aspects of sleep. So sleep exists in two rhythms, both as an ultradian, a non-REM rhythm, which happens about every 90 minutes. And there is a circadian, or 24, aspect of this rhythm, as well. Many of us have had experience with, if you've ever experienced jet lag, you know it has a profound effect on your behavior and ability to be alert, and how you feel emotionally and affectively. Dr. Lee also talks about life span, developmental changes in sleep. We know that young people and senior people sleep differently. Some of this is normal, some of it is not. And we know that we have some behavioral control over our ability to sleep and feel rested. And this is referred to as sleep hygiene, and she describes that at the end of her lecture. The class concludes with a lecture by Dr. Thomas Roth of Henry Ford Hospital. Dr. Roth focuses on daytime sleepiness and sleep need. The learning points in this slide are showing his emphasis on sleepiness as it's common in the general population. And sleep-related car accidents as a significant public health concern, as emphasized by this dramatic slide. And that sleepiness is regulated by multiple factors. These include things like the duration and quality of nocturnal sleep on the previous night. Circadian rhythms that we just talked about. Central nervous system acting drugs. And, of course, that includes the most commonly taken drug for altering sleep and wakefulness, and that is caffeine containing products. And, finally, central nervous system pathology. I hope this overview has given you some feeling for what the class will cover. For those of you who do sign up for the class, I think the first hurdle will be to get past the neurobiology section, if you don't have a background in neuroscience. But let me point out that that will be worth it because sleep turns out to be a wonderful vehicle for teaching neuroscience, both in terms of brain anatomy, cellular function, neurotransmitters, neural excitability, and so on. We look forward to having you join the class, and look forward to your feedback on Sleep: Neurobiology, Medicine, and Society. Thank you very much.
