Okay, now let's turn now to our discussion of how do you measure sleepiness. As you all know in research, something does not exist unless you are able to measure it. So the question becomes before we can discuss the morbidity in cause of daytime sleepiness, how do you measure it? One of things that's very important to understand is many people don't know they're very sleepy. So what we have here is 384 patients, information on 384 patients. These are all patients who have sleep Apnea. They're all interestingly enough, or virtually all of them deny being sleepy at all. But when we ask them, "What makes you sleepy?" Well, 91 percent of them say, "Well, watching television makes me sleepy." 85 percent said reading a book makes you sleepy. And I suspect everybody in this audience would agree with all of these things which people think that make you sleepy. In fact, none of these things make you sleepy. Later on, we'll talk about causes of daytime sleepiness. Boring lectures which you all have to attend don't cause sleepiness. Watching television doesn't cause sleepiness. You know, one of ways to think about this is these things don't cause sleepiness, they unmask it. They bring it to the surface and people are sleepy. Let me give you an example of a hypothetical experiment. So let's take a hundred third year medical students who are sleep deprived. And we sort of bring them into an auditorium at two O'clock in the afternoon, and we give them a lecture with a hundred histology slides and give them a lecture for one hour in a total monotone. How many of those students will fall asleep? I think we'll all agree that virtually all of them will fall asleep. Now, why did they fall asleep? Because of the boring lecture. So, in any experiment you always have to have a control groups. I'm going to have a control group of pre-adolescent children. So, the question becomes I'm now going to bring 100 six-year-olds. And for those of you who've seen six-year-olds, remember when you were six year old. I want you to think about this and bring in the same auditorium, same time, the next day, in the same hundred lectures, same hundred slides. How many of them will fall asleep? None of them. They'll become irritable, they'll run around, they'll poke each other, they'll misbehave quote and quote. And the reason for that is they're bored. Now the normal thing to do when you're bored is to find something to do. If you are not fully alert like our medical students, the thing you find to do is catch up on your sleep. So what makes the medical students sleepy in that classroom? What makes them sleepy or these apnea patients watching TV or reading? What makes them sleepy is fragmented sleep, lack of sleep. And that's what makes them sleepy. Their boring lecture just unmasks that sleepiness and sort of is permissive for their falling asleep. But if you're fully alert, you will stay awake in the most boring lectures known to man. Okay. Now, those questions which we had in our study were formalized very systematically by Dr. Johns and this is a paper he did, and this is called the Epworth sleepiness scale. And in this scale he asked people over the last couple of weeks, what are the chances you'd fall asleep? And the first question is sitting and reading, second is watching television, going down, they're all lying down in the afternoon, sitting quietly after lunch, in a car while stopped at traffic, and you can say the 0, 1, 2 and 3, and very, very clearly, zero as I would never doze off in a situation. Three, I would. And again, most of us who score some level of there. You can google this and fill it out for yourself. But anybody who has a score of greater than 10 is in fact sleeping. So a score of greater than 10 on the Epworth sleepiness scale is an indicator of sleepiness. It is actually the clinical, it is the most commonly used clinical tool for evaluating sleepiness. And these are some of the patient populations which have been used with Epworth sleepiness scale. So patients with narcolepsy have scores of about 17, patients with severe sleep apnea have scores of about 16. Interesting enough patients with Parkinson's disease are sleepiest patients with narcolepsy. Interestingly enough, people with seasonal affective disorder or major depressive disorder complaining of sleepiness, they do have sleepiness while most depressed patients, they really don't have sleepiness or even when they complained about the more are fatigued unless again talk about sleepiness but really they're fatigued. And one of the things you sort of have to understand which I think is critically important, if you're going to study sleepiness and you can do it at a subjective level, it's very important to differentiate three different biological states but which whose descriptors are used interchangeably by people. We have sleepiness, which we talked about the physiological basis of that. We have fatigue which can be muscular or mental fatigue, or we have depression where people complain about fatigue. So those are three things which are very important to differentiate. But very clearly, we don't have to measure sleepiness subjectively, we can measure it as an output. And there are a variety of behavioral measures which people use. So for example, people use memory tasks, people use psychomotor performance tasks, people use executive function tasks, but psychomotor task are the most commonly used ones. Things like reaction time. Now what makes the tasks very sensitive to sleepiness if it's long? Any of us can do anything for about a minute a two minute, but take them sleepiest person that we ever interviewed to sort of say look, if I keep you, if you stay awake for the next two minutes, I'll give you $1,000. They can do it. If I on the other hand I do that for the next two hours, they can't do that. It's got to be a monotonous task. The more monotonous the task, the greater the likelihood. Because remember we said one of the things that keeps us awake is motivation. If you're not motivated externally paced. So for example, if I have to work on an assembly line, let me give an example. I give somebody a hundred mathematical problems, who's been sleep deprived for a couple of days. If I give you one mathematical problem every second on the screen, periodically you'll miss a problem because you have dozed off for second. On the other hand, if I give you a hundred mathematical problem to work at your own pace, you'll get them all right, because when you get sleep, you just nod off for a minute. And again no feedback. If you don't know how you're doing, you're more likely to not be motivated and do poorly. So again, psychomotor task is very sensitive if they're long monotonous externally paced without feedback. What's a good example of that kind of task? Driving a car. We'll come back to that. You drive your car down in a hurry for an hour. It's a monotonous task. You don't get to decide when the road turns, when somebody stops in front of you, and you don't know how you're doing until it's too late. So very clearly lots of tasks. And here's an example of driving. So, in here we have, we'll talk about changes in reaction time in milliseconds. So what happens if a change reaction time? I keep you awake and I increase your reaction to about 100 milliseconds. What does that mean? Well, if you're driving at 70 miles an hour, that means you're going to stop 10 feet later, which means you'll be off the road or in the car in front of you. So at 70 miles an hour, very, very short changes in reaction time have very, very profound consequences. Now we also measure sleepiness physiologically. We do a lot of work on roll potential. Many of the car companies have looked at rolling on movements. One of the things which measured sleepiness or sleep onset is in fact rolling eye movements. David Yubell did a classical study where he showed that the minute we fall asleep is the moment, and this is arguable, when we start processing visual information in geniculate body, and what we see is rolling eye movements rather than conjugate rapid eye movements. Pupillometry with its measure in order to know nervous system is e.g. spectral activity things like alpha activity and beta activity are measures. But the most commonly measured, most common measures of sleepiness are something called the Multiple Sleep Latency Test and a related test called Maintenance of Wakefulness Test. The multiple sleep latency test is magnificent in its sensitivity and in its simplicity. It is a test which is very, very simple to understand. And we'll get to that in a minute. The other thing is we said, is you can look at brain activity. Remember we talked about you have to have all of these innovations in the cerebral cortex. Well this is somebody who had been sleep deprived for 24 hours. And if you look at the pre-frontal cortex, all those stimuli in the thalamic areas, all those stimuli which are supposed to keep us awake do not do that. But let's go back to the multiple sleep latency test. So this is a person which is one of those severe sleep apnea actually we talked about. We put to bed at 10 o'clock, and remember we talked about EEG activity changes. So this is Alpha where this person is wide awake. This is three seconds, six seconds, nine seconds. So at 10 o'clock after nine seconds, this patient who denies being sleepy falls asleep. And you can see, he's clearly falls asleep. And here actually, you start seeing the beginning of rolling eye movements. It's a lot of these things coming together. So this is a person who does not feel sleepy. But as soon as you lie him down in a dark room, he falls asleep in nine seconds. This is a group of normal healthy volunteers. We put them to bed every two hours as the multiple sleep latency test requires. And you can see at 10 o'clock when that person falls asleep in three seconds, a normal person takes 15 minutes. Remember this circadian pacemaker, the homeostatic drive builds up. Well, about two o'clock in the afternoon when we think food makes us sleepy it's not true. It's that time of day and we all get sleepy by two o'clock, and after where sleep latency is about nine minutes. And then, that circadian pacemaker kicks in and gets us awake. So what we see is the average person across the 24 hours, will have a mean MSLT or means sleep latency of about 11 minutes. That's a normal person. As I'll show later on, apnea patients will fall asleep about three or four minutes. Our children remember those pre-adolescence, they go in bed for 20 minutes and they say, now what do you want me to do Dr. [inaudible]. So, they never fall asleep. They're awake all for 20 minutes. Now, all of the things we talked about a very highly related. So this is the multiple sleep latency test and this is performance. This are those lapses, remember I was doing math problems and you stopped doing them. And you can see, this is the days of not getting adequate sleep. And you can see, as you get more and more sleepy, your performance on this vigilance task goes down. So very clearly, these are not different measures but they're really very, very similar measures. So we've sort of seen that we can measure sleepiness in a variety of different ways. And ideally, in research we measure more. We can measure physiologically with multiple measures. We can measure them cognitively or psychomotor performance for memory tests, and we can measure by asking the subject or the patient how they feel. So with that, we are now going to turn to talking about, what is the prevalence of daytime sleepiness? What percent of our population is sleepy and what is the consequence of that?