Welcome, to the wrap-up for Lecture 5. Today sitting here in the kitchen of the institute with us is David Lenssen, one of your TAs for the course and a PhD student in the institute. Neda Ghotbi, a medical student, who is doing her doctoral thesis here in the institute. Joana Matera, a PhD student who's just finishing up her work as a student with Till. And Luísa Pilz who is a student from Brazil, who's doing a PhD between Munich and Brazil also with Till. And Till is here, your teacher. So I would like to say one thing right at the beginning, that you've heard a lot today in the lecture about the MCTQ, the Munich Chronotype Questionnaire. And if you go to the homepage of this course, we'll make sure that there are directions or link directly to the MCTQ, and we suggest that you actually go and, and fill it out. If you can manage to remember to do it, please put Coursera into the referral field when you're asked where or how you were referred to the questionnaire. And then this actually might be something that would be interesting to discuss in the discussion forum. You'll get feedback on what your chronotype is. And I think it could be really interesting if people discuss in the forum why they think they're a particular chronotype, is it more the light, the genes, or whatever? >> And let me say that you don't have to put in your names. >> Absolutely. >> You don't have to put in an email address. But if you don't put an email address into the field you cannot get the PDF that we send out as the answer to the questionnaire. >> So couldn't we reveal the determinants of chronotype? >> Of course we can! Well, in general the most important ones are genes, for example. Then also age: People tend to become earlier chronotypes when getting older. and are around their adolescence very late in chronotype. Then, the next would also be sex. Between female and male there are differences. And also the light environment. These would be the general aspects that you have to consider. Between populations though, we have things like lifestyle. Think about for example, the way you work, or how you live. Then also seasonality, of course, and living in rural or urban places, which might be considered also lifestyle but would also be something that you would have to take into account. >> So, why is it important for people to tell us when they fill out out the MTCQ? >> Mm-hm. Yes, that's very important. So we need to know where exactly on earth you live. For example it can be completely different if you live on the northern hemisphere. There might be summer. But where you come from, from the southern hemisphere, there might be winter. So it's important for us to know in which photoperiod you live. And humans entrain to suntime, so we need to know which photoperiod you're actually living in. >> I think that it's really interesting to look at the dataset. I think David has actually had quite a lot of experience with this, where you have a big dataset with MCTQ, with chronotype information or time of day information. And then when you correct that not only for time zone, but for where within the time zone people are living, then you see that the results become much clearer. >> Yes. >> Which is another indication of the entrainment to suntime. >> And you could do fine things if you actually look at a certain readout, which you would expect to be related to sun, if you would look at the northern hemisphere then you would predict an opposite effect on the southern hemisphere. >> Mm-hm. >> So you can do some nice, natural experiments. >> That's right, you can use this information to actually build hypotheses and tests, make tests to test you hypotheses. >> And all this is easy if we have a postal code because there are very good data banks where you can look up from the postal code exactly- >> Yeah. >> what latitude and what longitude that position is, in and also what position it is within the time zone. Is it the Eastern border or the Western border of the time zone, and all these things are important. >> Okay, so if someone has an extreme late chronotype and for example if they would like to change it and modify it, how would they go about it and what are the rules? >> So we know that light has an important role in adjusting our internal day to the external 24 hour day. So if you are an early person you will like to expose yourself to light more in the second half of the day so that you can fall asleep later. But if you are an extreme late person, you should do the opposite. You should expose yourself to more light in the first half of the day and then less in the second half. >> So this is also shown, for example, so many people nowadays use these modern techniques, modern devices like pads, phones, computers with screens... >>And televisions. >> Of course, televisions in the earlier days. With close distance to the screen. And the screen emits a lot of blue light and we know that that influences the clock, as you said. So using this later the evenings might actually influence your sleep. >> So, fortunately, we've heard a lot about these new devices and apps that are out there that actually reduce the amount of blue light coming from these screens. And so one solution, of course, is to turn off the computers, and pads, and phones and so forth, at night, and that's an interesting concept. The other solution for those who really can't bear to do this is to get one of these apps that cuts out the blue light, so that you can still continue to work into the night without pushing your face. >> And I think there are also filters which you can stick onto the screen- >> Physical filters? >> Physical filters. >> Yes. >> But if nothing of this helps and you really have to become earlier, the best thing is to be, as much as possible, in the evening in darkness, even if you can't sleep. And one can do a lot of thinking in the darkness if one knows that one doesn't have to fall asleep. But this darkness alone will make you wake up earlier. >> So what is morningness and eveningness, and how can we compare that to the chronotype we're measuring with the MCTQ? >> So chronotype is something that has been measured by psychologists for many, many decades, actually. And they approached it in a way that they wanted to know what the preferences of people are. >> Mm-hm. >> And there was a theory that we have two types of people, the morning people and the evening people. And the Morningness-Eveningness Questionnaire was actually invented to distinguish between these two types. The Morningness-Eveningness asked you questions of what you would like to do according to your feeling best rhythm. When you would like to do sports, when you would like to sleep or be active, when your best time for mental performance is, when you eat, and not eat. So, it's a huge variety of different questions that come into a score. So many psychological questionnaires result in a score. And the higher your score in the Morningness-Eveningness, the more morning people you are, the more morning person you are. And if you have a low score then you are an evening person. Now that's a completely different approach to what the MCTQ does because the MCTQ wants to compare people in their phase of entrainment and it uses the sleep times to estimate what the phase of entrainment is in reference to, for example, suntime. So it's two different approaches, they´re both chronotype, and they both correlate. Because of course people who are late types based on their entrainment are also those who fill out that they would like to do things later. And therefore they correlate, but they are not really translatable. >> So the MCTQ also asks work and free days separately? That's an important point. >> It's a very important point because of course, if we want to know where the phase of entrainment is we should not look at those days where we have to get up with an alarm clock. Because in the minute we use an alarm clock, we have an artificial get-up. And it's not exactly apt to find out where the middle of your natural sleep period is. >> And what I've observed also is that whenever you ask people about the timing of their behaviour, it's of course different on workdays and free days, it is for all of us. And if you don't specify what you're asking for, you get some people who are putting in work days and some who are putting in free days. Perhaps dependent on which day they answer the questionnaire, and so it's really a mixture. >> Well, probably not even that. Most people answer what they usually do because they are asked what they usually do. And since most of us have more work days than free days and they answer what they do on workdays because that's what they usually do. >> So they're both subjective questionnaires. They're both asking for people to interpret their behaviour but one of them has really, as you said, a very psychological set of questions and the other one is really asking people to recall numbers, when in the day they did certain things. >> I mean, in a way, asking you how tall you are is also a subjective question. >> Yes, exactly, this is what I'm getting at. Yes, it's very subjective, but it's also almost objective, right? >> Mm-hm. >> Indeed when you looked at actimetry compared to what people report, there's a very high correlation. >> Yes. >>One more little thing on that. I am always so fascinated by this thing that if you ask a huge amount of people a certain question that the answer somehow regresses to the mean. So if you ask a lot of people then somehow it comes very close to the real answer. >> Yeah, because if you have a bit of biological basis for the answer of the question, and people get the answers wrong, or they lie, they will lie in all kinds of directions, whereas the biological basis comes out from all those many people who don't lie. So it's the ones who lie or don't know the answer... [CROSSTALK]- They don't know the answer, they go in all directions and, therefore, they can't reason on their own. And in the end, you come up with a biologic determinant, which is so nice in big numbers, but only in really big numbers. >> Mm-hm. >> So then, I want to have the question what physiological phase markers have been actually used to determine the entrained phase of the clock? >> Well, there are many for starters. But we might want to concentrate on a few. For example, the most popular, I would say, is melatonin. And melatonin is actually a hormone, that is produced in the body. And it rises as soon as the sunlight diminishes in the evening. And melatonin is referred to as a sleep inducing hormone actually. So it would make sense to rise in the evening. And the time when you can actually detect melatonin is called the dimlight melatonin onset, because, see, during the day, when there's a lot of light out there, melatonin is undetectablely low, or absent even. So, that would be one phase marker. >> Mm-hm. >> The other would be, for example, core body temperature. Of course, core body temperature, it is difficult to measure it. Because, you know, it's pretty invasive to measure it in people. And sort of, it's also very busy, you know, the data that you get. But core body temperature, of course, changes during the 24 hour day. And then is at it's lowest at four, I think, around 4 AM, which is also actually the midpoint of sleep for most humans. >> Mm-hm. >> So it gives you a nice correlation like that. >> Right. >> But there are, of course, other things, like heart rate >> Right. >> or steroids. >> Indeed I think you hit on one of the problems of the business or the noisiness of the data with the temperature rhythms: the more people are active the more there is sort of noise that's imposed on top of this circadian rhythm in body temperature. And that's one of the reasons it is not very much used, I think, in many experiments, it's used primarily in these highly controlled experiments where people are really, really lying down. I think even sleep interferes somehow with the circadian rhythm of core body temperature. So many of these outputs are a bit complicated because of this masking from activity. And that's why melatonin is pretty well appreciated. That, except for interference from light, it seems to be quite robust. And I would add in addition to what you said, it's not going to be increased if you have a lot of light outside. That's true. It sort of gets degraded when you're exposed to light. But it doesn't follow that it always comes up when the light goes down, when the sun goes down, because that, of course, depends partly on your chronotype, and earlier chronotypes will have an earlier onset and later chronotypes will have a later onset. And that's why in the lab they put people into dim light conditions and I even have heard about experiments where you go into the real, real world and do experiments. You just keep people in dim light for the evening and then they collect saliva over the course of the evening to test it for when their melatonin onset is. >> Well, that's why it's called dim-light-melatonin-onset. >> Exactly. >> Because you have to have them in dim light. It's a very little gradual increase of your melatonin which you want to catch and to use that phase to comprepare it, for example, to chronotype. I also wanted to addthat, of course, you Neda as a doctoral student of the medical field think about humans when you think about melatonin, and therefore you think it makes us sleep. But of course, melatonin as a hormone is much older, and we mammals have all gone through the nocturnal bottle neck, meaning, we are descendants of nocturnal animals. >> Right. >> And that rhythm in nocturnal animals is exactly the same. It comes out during the night and it comes down during the the day where as the nocturnal animals are, of course, active during the night and sleep during the day, so for them melatonin means internally something completely different for their physiology and behaviour than it does for day-active animals like us. >> So, just one more comment to that discussion is that last year at the rhythms meeting of our entire field last June in Montana, there was a whole workshop on phase markers and what can we use for them, and, and how can we get more of them? And so this is really a big problem in our field. It's acknowledged that we need more than one or two good ones. And we're still looking. I think that with a lot of the "-omic´s" studies that are being done showing metabalome components that are rhythmic on a huge scale, I mean many, many, many of them, hundreds of them and proteins, I think that we are going to find some markers that are not masked by activity, and that are going to be really good robust phase markers. So I think we're edging towards that but we certainly need more than just the two that we have. >> And especially those that work in the field. >> Yeah, yeah so people can be walking around doing things and then blow into something or spit into something and then get some data back from this. Good. I think that we probably have said enough today for this wrap-up. We don't want it to go on longer than the Lecture itself. And so we look forward to seeing all the students back next week for the Sixth Lecture on Pathologies and the Clock. And now I hope that you will finally take some Krapfen and help me eat these things. >> Mmh. >> I'll take this one. 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