Welcome to the lecture on human circadian clocks in real life. On several occasions we have introduced the experiments in temporal isolation. For humans the first of these experiments were performed in the famous Erling "Bunker" that Jürgen Aschoff and his colleague Rütger Wever built into a hill. We have also seen the following graph before in slightly different versions. The horizontal axis at the bottom represents the local time and the vertical axis represents "the days of the experiments" that a subject spends in the bunker. During the first week, the doors of the bunker were open and the subject had access to clocks and watches and could go outside to see daylight or darkness. This entrained part of the experiment is indicated by the grey and the yellow background. During that time, the subject went to sleep and woke up at their own will, as represented here in form of purple bars. As you already know, the regular alternation between wake and sleep continues when the door of the bunker apartment is closed so that the subject has no more access to light or time information. The only thing that changes is that subjects don't live exactly 24 hour days anymore. In this case shown here the subject lived an approximate 25 hour day, as can be seen by the sleep times getting later and later over the course of the experiment. To make the graph less busy, we just draw a regression line through the midpoints of the sleep episodes and then remove the sleep representing bars. If we now add more mid-sleep lines, from different experiments and subjects, we see that some people live even longer days in the constant conditions of the bunker (represented here by the red line) while others live shorter days but still longer than 24 hours, (represented here in the blue line). Very few people actually live bunker days that are shorter than 24 hours (represented here by the purple line). You may have noticed that there is a systematic relationship between the timing of sleep while the subjects were still entrained to the 24 hour light dark cycle and the length of the days, they produce when they are released into the constant conditions. The later their sleep times during the "normal" first week, the later their so-called chronotype, the longer their internal days during the free-run. Laboratory experiments - especially with human subjects, are extremely labor intensive and expensive. We have learned an enormous amount about the circadian clock by controlled laboratory experiments. But we need to take research into the real world to verify if the insights we had in the lab are also valid in every day life. One of the approaches to collecting information about a system in the real world is epidemiology. And the research instruments of choice are questionnaires. In the previous graph, you have seen the individual differences in sleep timing and that they are obviously tightly coupled with the circadian clock. After all, they systematically represent how the circadian clock will behave in constant conditions. We therefore use sleep timing to ask as many people in the real world as possible and developed a simple questionnaire that asks people about their sleep times. The Munich Chronotype Questionnaire, MCTQ for short - asks simple questions about people's sleep behavior. Since there are often misunderstandings between bedtimes and sleep times, we decided to accompany subjects through the night. To be even more sure to avoid misunderstandings we provide little drawings to clarify what we mean. The first question asks when people go to bed. The second picture reminds subjects that many people do something in bed before they decide to go to sleep at a time which is probed by the next question. The next question wants subjects to estimate how many minutes it takes them to actually fall asleep. Followed by asking them when they wake up and eventually when they get up. These questions are asked separately for work days and free days, such as weekends. Subjects should answer all questions by averaging their typical behavior on normal work and free days. It is also very important to know whether people are woken up by an alarm clock or other means that insure that one gets up at a certain time. We have meanwhile collected more than 200,000 entries in the MCTQ database. This map shows the geographical distribution of these entries. By far the majority of entries comes from Germany where the MCTQ was initiated, but also from other countries in central Europe. The United States are catching up fast. And we also have a rapidly growing number of participants from Australia and other parts of the Southern Hemisphere. The worldwide studentship of Coursera, will hopefully help to fill the empty spaces on this map. So please tell all your friends, colleagues and family members to fill out the MCTQ at this web address. It is remarkable how many variables can be calculated from these few questions. Let's go through an example. If our subject goes to bed at midnight and gets up at 10:00 A.M, then the total time in bed is ten hours. Our example subject decides to go to sleep at half past midnight and needs about half an hour to fall asleep. Sleep onset in this case is therefore at 1:00 a.m. The subject indicates to wake up at 9:30 a.m. Which provides us with the sleep duration. We also know the time it takes to fall asleep, which is called sleep latency. And the time this person stays in bed before getting up which is an indicator for sleep inertia. Sleep inertia refers to the time after wake up when people are not really awake yet. It can last of course longer than the time one stays in bed, especially on work days, when people have to get up. We also know an additional, very important variable. And that is mid-sleep, the time halfway between sleep onset and wakeup. This point is very important for estimating chronotype. You will see later in this lecture that sleep timing and sleep duration are independent traits. Among early chronotypes, there are as many long and short sleepers as among mid chronotypes. One can, therefore, not use sleep onset or sleep offset to assess chronotype, because they depend very much on how long a person sleeps. The midpoint of sleep turns out to be the best time reference that one can use to estimate choronotype. And it is self explanatory that we are interested in the mid sleep point on free days, and more importantly on those free days when people wake up by themselves rather than by an alarm clock. We call the mid-sleep on free days MSF, and the distribution of MSF meanwhile represents more than 200,000 people from all over the world, who have filled out the MCTQ. MSF is already a good base for assessing chronotype or individual internal time but there is a complication with the sleep on free days following a work week. Let's go through another example. This subject falls asleep on work days sometime between 11 p.m and 1 a.m and wakes up quite obviously with an alarm clock at around 6 a.m. The average mid-sleep time on workdays, which we call MSW, is five minutes past 3 a.m. On the weekend, things drastically change. The example subject falls asleep sometime between half-past one and half-past two and wakes up sometime between 10:30 and noon. The average mid-sleep time of free days, which we call MSF, is slightly before half past 6 a.m. The average sleep duration of workdays, is just under six hours and that on free days averages nine hours. Across the entire seven day week, this subject averages close to seven hours. But on free days, he or she sleeps around nine hours. The long over-sleep on weekends is due to the significant sleep deprivation accumulated over the work week, where the subject gets almost an hour less than their weekly average. So by the end of the work week, the subject has slept about five hours less than average. Under these conditions, we have no way of knowing the exact sleep need of this person. I even would say that we so far have no way of objectively knowing the sleep-need of any individual. So the average sleep that people get across the week is as close an estimation as we have towards this important variable sleep need. We can now estimate how much of the sleep on weekends is close to an individual's sleep need and how much is recovery sleep. The mid-sleep time on free days is therefore a combination of recovery sleep and the circadian regulation of sleep timing. But our aim here is to estimate an individual's internal mid-sleep or internal midnight as closely as possible. We therefore have to correct MSF by the amount of over-sleep, which moves the MSF in most cases a bit earlier. This transformation gives us a new variable, MSF corrected for over-sleep or MSFsc. You have probably noticed that the distribution of MSF is slightly over represented at the late part on the right. This is partly due to the fact that the later an individual's chronotype the larger the sleep loss during the work week and the longer the oversleep on weekends. The skewedness of the distribution becomes much smaller when we correct MSF for the oversleep. This graph shows the distribution of MSFsc. [SOUND]
