Categories
Circadian science Lighting

Tis the Season: Seasonal Effects and Circadian Rhythms

As today is the shortest day of the year in the Northern Hemisphere (and the longest in the Southern Hemisphere), it seems appropriate to talk about how the seasons change our bodies’ rhythms. Many things change with the seasons, but the main seasonal variation that I will consider here is the variation in day length. 

The seasonal variation in light duration is a big change experienced as you move away from the equator. 

A contour plot of the number of hours of daylight as a function of latitude and day of the year. (Courtesy Wikipedia)

Growing up in Texas, I didn’t really appreciate this variation, but during my graduate school years in Michigan, I experienced it first hand. Personally, the short winter days were a bigger adjustment than the temperature. It felt like anytime I had to drive it was dark and snowing. 

Seasonal changes are known to induce all kinds of physiological changes in our bodies. These include changes in the immune system (Nelson and Weil 2015), physical activity (Shephard and Aoyagi 2009), weight gain (Baranowski et al. 2014), and hormonal changes (Tendler et al., n.d.). Even hair growth changes with the seasons (Shephard and Aoyagi 2009; Randall and Ebling 1991). 

One of the more surprising seasonal cycles is that human reproduction varies seasonally. So called “birth pulses” have been found to occur seasonally within the United States (Huber et al. 2004). Suicide numbers peak in the late spring/early summer. This is also the time of year associated with peaks in aggression and violent acts such as homicide and mass shootings (Geoffroy and Amad 2016). 

Figure taken from Stevenson et al “Disrupted seasonal biology impacts health, food security and ecosystems”, Proceedings of the Royal Society B, Oct 2015. (a) Show the suicide rates in Japan (b) Minor assaults in England and Wales.

Historically, battles and other aggressive behaviors have been shown to peak in this season as well. With all of these seasonal variations, it is natural to ask how the body keeps track of the seasons. Also, what does this have to do with circadian rhythms and the mission at Arcascope? 

First, a bit of background. Our daily rhythms are driven by biological clocks found throughout the body. The most important of these clocks is the central circadian clock located in a region of the hypothalamus called the suprachiasmatic nucleus (SCN). The central clock coordinates and synchronizes the other clocks found throughout the body, and—importantly —the central clock receives light information directly from the eyes. These light signals are the primary mechanism by which our bodies’ internal clocks stay aligned to the outside world. 

It turns out that this central clock is also responsible for maintaining the body’s record of seasonal information (Hannay, Forger, and Booth 2020; Coomans, Ramkisoensing, and Meijer 2015). It is both a daily clock and an annual calendar. This means the core clock has to somehow maintain a longer-term memory of the light it has seen over the past weeks and months. After all, you wouldn’t want to switch into winter mode just because of an especially cloudy afternoon in July. 

The daily 24-hour clock can be found ticking inside each of the individual neurons in the SCN. By averaging across these neurons at the population level (there are around ten thousand of them), you can arrive at a consensus daily time. The seasonal clock seems to work differently: important parts of the seasonal calendar are stored at the population level. This means each individual cell doesn’t know if it is July or January, but if you look at the whole population you can see seasonal changes. In other words, while the daily clock is stored by the consensus or average of the individual clocks, the seasonal information is encoded in the spatial patterns of the clock neurons. 

Interestingly, the seasonal patterns can also feed back on the daily clock and change how it operates (Pittendrigh and Daan 1976). For example, keeping lab animals in summer or winter conditions is known to cause lasting changes to their circadian clocks (the intrinsic period of the clock). These changes can persist for months after they have been moved into a different lighting environment. Another example is that mammals kept in lighting conditions close to long summer days are less light-sensitive than those kept in winter conditions (Pittendrigh and Daan 1976; vanderLeest et al. 2009). One explanation is that the clock needs to be more sensitive to light in the winter for the obvious reason that less light is available (Hannay, Forger, and Booth 2020). 

In modern life, our light exposure patterns do not differ as widely across the seasons due to artificial lighting. In fact, the average light exposure is closer to a perpetual summer (Wehr 2001). This perpetual summer environment has been found to maintain a summer-like state in the melatonin cycle (Wehr 2001). This movement towards perpetual summer has likely suppressed seasonal cycles which are important to maintaining health (Wehr 2001; Stevenson et al. 2015). Mice kept in constant artificial light have been found to have bone deterioration, reduced skeletal muscle function, and disrupted immune function. In humans, it has been shown that natural lighting conditions (camping) leads to a lengthening of the biological night during the winter months (Stothard et al. 2017). 

It is clear that the seasonal variation is important to our health and that modern artificial lighting is disrupting those cycles. On top of that, the long-term memory of light exposures means that these seasonal changes can also affect the operation of the daily clock. At Arcascope our core mathematical models are built to incorporate these seasonal variations— all as part of our goal of helping people maintain healthy daily and seasonal rhythms. 

Citations

Baranowski, Tom, Teresia O’Connor, Craig Johnston, Sheryl Hughes, Jennette Moreno, Tzu-An Chen, Lisa Meltzer, and Janice Baranowski. 2014. “School Year versus Summer Differences in Child Weight Gain: A Narrative Review.” Childhood Obesity  10 (1): 18–24.

Coomans, Claudia P., Ashna Ramkisoensing, and Johanna H. Meijer. 2015. “The Suprachiasmatic Nuclei as a Seasonal Clock.” Frontiers in Neuroendocrinology 37 (April): 29–42.

Geoffroy, Pierre Alexis, and Ali Amad. 2016. “Seasonal Influence on Mass Shootings.” American Journal of Public Health.

Hannay, Kevin M., Daniel B. Forger, and Victoria Booth. 2020. “Seasonality and Light Phase-Resetting in the Mammalian Circadian Rhythm.” Scientific Reports 10 (1): 19506.

Huber, S., M. Fieder, B. Wallner, G. Moser, and W. Arnold. 2004. “Brief Communication: Birth Month Influences Reproductive Performance in Contemporary Women.” Human Reproduction  19 (5): 1081–82.

Nelson, Randy, and Zachary Weil. 2015. “Faculty of 1000 Evaluation for Widespread Seasonal Gene Expression Reveals Annual Differences in Human Immunity and Physiology.” F1000 – Post-Publication Peer Review of the Biomedical Literature. https://doi.org/10.3410/f.725486269.793507034.

Pittendrigh, Colin S., and Serge Daan. 1976. “A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents.” Journal of Comparative Physiology ? A. https://doi.org/10.1007/bf01417860.

Randall, V. A., and F. J. Ebling. 1991. “Seasonal Changes in Human Hair Growth.” The British Journal of Dermatology 124 (2): 146–51.

Shephard, Roy J., and Yukitoshi Aoyagi. 2009. “Seasonal Variations in Physical Activity and Implications for Human Health.” European Journal of Applied Physiology. https://doi.org/10.1007/s00421-009-1127-1.

Stevenson, T. J., M. E. Visser, W. Arnold, P. Barrett, S. Biello, A. Dawson, D. L. Denlinger, et al. 2015. “Disrupted Seasonal Biology Impacts Health, Food Security and Ecosystems.” Proceedings. Biological Sciences / The Royal Society 282 (1817): 20151453.

Stothard, Ellen R., Andrew W. McHill, Christopher M. Depner, Brian R. Birks, Thomas M. Moehlman, Hannah K. Ritchie, Jacob R. Guzzetti, et al. 2017. “Circadian Entrainment to the Natural Light-Dark Cycle across Seasons and the Weekend.” Current Biology: CB 27 (4): 508–13.

Tendler, Avichai, Alon Bar, Netta Mendelsohn-Cohen, Omer Karin, Yael Korem, Lior Maimon, Tomer Milo, et al. n.d. “Human Hormone Seasonality.” https://doi.org/10.1101/2020.02.13.947366.

vanderLeest, Henk Tjebbe, Jos H. T. Rohling, Stephan Michel, and Johanna H. Meijer. 2009. “Phase Shifting Capacity of the Circadian Pacemaker Determined by the SCN Neuronal Network Organization.” PloS One 4 (3): e4976.

Wehr, T. A. 2001. “Photoperiodism in Humans and Other Primates: Evidence and Implications.” Journal of Biological Rhythms 16 (4): 348–64.

Categories
Circadian science Technology

Yesterday’s Weather

I love my Apple Watch.

The ability to track my exercise, heart rate, activity levels, and sleep has enabled a real awareness of how my physical and mental health changes over time. The ability to track personal health data over long time periods outside of laboratories is one of the most exciting developments of the last decade. I believe this data will usher in a new era of personalized, precision health which just wasn’t possible in the past. At Arcascope, we are at the forefront of developing algorithms to turn the data collected by wearable devices into insights that improve people’s lives. 

With that being said, the current state of things just isn’t all that satisfying when you think about what’s being left on the table. So much of the data being collected is uninterpretable. Knowing my current heart rate is cool, but what can I do with that information? The part of this that bothers me the most is that so much of this data is focused on the past. 

Here is a screenshot from Apple Health showing my sleep over the last month. You can see that I had some wake periods at 3 am at the beginning of the month. But how does this information really help me? 

Sleep tracking in particular reminds me of a weather app that can only tell you yesterday’s weather. Clearly, a weather prediction service that could only tell you the weather from 24 hours ago wouldn’t do well against the Doppler radar. It is useful to be able to say exactly how hot it was yesterday, and interesting to know how that compares to years past, but I really want to know if I should bring an umbrella with me when I leave the house. 

I can tell that I didn’t sleep well last night from the fact that I am feeling tired. Having a device to quantify exactly how poorly I slept can be useful for tracking long-term trends, but it isn’t all that useful on a day-to-day basis. 

Another snapshot from my Apple Health data. Doesn’t this remind you of a weather app pointing out how this weather’s month compares to historical trends? What about today? Or how about tomorrow?

Okay, enough of the weather prediction analogy. I’ve already pushed that analogy further than I should. First, unlike the weather, we actually have control over our behavior, and what we are doing now will change the forecast for our physiology tomorrow. Also, these variables are much more predictable than weather. 

The technology we have developed at Arcascope can answer questions like: 

  • What separates the days where I am at my best, from the ones where I am struggling? 
  • How can I alter my behavior now so that I will sleep better tonight?
  • When is it best for me to stop drinking coffee for the day? 
  • When will it be best for me to study, exercise, eat and relax? 
  • When is the best time to take my medication to minimize side effects? 
  • When should I avoid high stakes activities because my chances of making a mistake are highest? 

We believe this is the future of personalized health tracking. We also think it’s a heck of a lot more exciting than looking back at yesterday. 

Categories
Circadian science Sleeping troubles

Signs of Circadian Disruption

In this blog post, I want to point to some common symptoms of circadian disruption.

The role of circadian rhythms in sleep is subtle, and many times issues that are attributed to other sources really have circadian factors as the root cause. 

The two process model:

To understand the interaction between sleep and circadian rhythms we need to discuss the two primary drivers of sleep: the homeostatic sleep drive and the circadian drive to sleep. 

The homeostatic sleep drive (called “Process H”) describes the build up of sleep pressure the longer you are awake. This drive builds up anytime we are awake, and the higher it gets, the harder it is to stay awake. In contrast, when we are asleep, the homeostatic sleep drive decreases. 

Let’s imagine what would happen if this were the only component driving sleep. Then people would operate a bit like my iPhone: Active as long as your battery lasts, then asleep/recharging as long as it takes to get back to full battery… or at least until you get yanked off the charger. 

If I wanted to adjust the “sleep schedule” of my iPhone I could just adjust the time that I pull it off the charger. I could also use it more (burn up the battery, turn the screen to full brightness) if I wanted to make it “go to sleep” sooner. This probably doesn’t match your experience with sleep. Being more active during the day doesn’t ensure that you will go to sleep earlier (although it can help). And staying up an hour later doesn’t necessarily mean that you’ll wake up an hour later the next morning. From experience, you’ve probably already learned that sleep duration isn’t just a function of how tired you were when you fell asleep. 

This is because the homeostatic sleep drive is one of the two processes which control our natural sleep cycles. An iPhone has no issues with jet lag, shift work or sleeping on Sundays! That’s because it doesn’t have…

Circadian Rhythms: The Second Process

The more subtle process which controls our sleep cycle is the circadian clock, also called “Process C”. Circadian rhythms in humans act to help us sleep in a single block at night by modulating the sleep drive according to the body’s internal clock time. Much more about this process below. 

So what are signs that your sleep issues are being driven by your circadian clock? 

  1. I wake up at 3am and can’t get back to sleep 

One of the most common sleep disturbances is waking in the middle of the night and not being able to get back to sleep. Very often circadian rhythms play a role in this annoying occurrence. 

We can think of the homeostatic sleep drive and circadian sleep drive as executing a delicate hand-off in the middle of the night. Let’s walk through what happens when everything is in sync.  Since homeostatic sleep drive increases whenever you are awake, the hours near bedtime are when the homeostatic sleep drive is at its peak , while the circadian sleep drive is opposing sleep– or at least not promoting it. This push and pull helps keep you awake through the evening hours even if you have had an active day. This also keeps your bedtimes consistent (and in a natural environment aligned with sunset).  However, once you fall asleep, the homeostatic sleep drive begins to decrease steadily, and soon it reaches levels similar to those you had during the daylight hours. So why do you stay asleep? 

Well, as the night progresses, the circadian process begins to take over the job of promoting sleep. This maintains an overall drive for sleep throughout the night. Finally, around dawn, the circadian drive to sleep drops enough for you to wake up. The handoff in the middle of the night between the homeostatic sleep drive and the circadian sleep drive is what allows for one, contiguous block of sleep. 

If your circadian rhythms are out of whack, this handoff can be fumbled, leading to the annoying episodes of waking in the middle of the night and not being able to get back to sleep. 

  1. Trouble getting to sleep on Sunday 

Another very common sleep disturbance is “social jetlag”. This is caused by the likely familiar practice of staying up later on Friday and Saturday night and sleeping in the next mornings. This move to later light exposures tells our circadian clock to shift later, so it creates the same effect as jet lag without you ever leaving the couch.

If you stay up three hours later on Friday and Saturday and sleep in a commensurate amount, you have effectively traveled from New York to Los Angeles for the weekend– a three hour shift west. The pain comes when you need to perform the reverse trip to get back on your workweek schedule. When you try to go to sleep at 10pm on Sunday night then, as far as your body is concerned, it’s  7pm. Worse yet: this will often move the Sunday bedtime into the dreaded wake maintenance zone, discussed next. 

  1. I try to go to bed a few hours earlier and I just can’t fall asleep 

This is caused by the so-called “wake-maintenance zone”: in the hours leading up to bedtime, there’s a period of time where it’s hard to fall asleep. From an evolutionary perspective, this wake maintenance zone, which would occur as the sun was setting, could have existed to ensure we’d be awake and active while we still had some light to make our way to a shelter (or into a tree) before nightfall. In modern life, bedtime is rarely sunset, and this wake maintenance zone can fall in the 9pm-11pm range. 

In conclusion: Your inability to move your bedtime up by a few hours may not have anything to do with mindfulness and have everything to do with how much sunlight you got the previous morning. 

  1. Whenever I am on a break from (school/work/obligations), I end up going to bed at 3am

This typically happens when the societal constraints that are keeping the circadian clock tethered to the sun are removed. Often,  someone on a spring break (and without any reason to set an alarm), will find that their schedule starts to  drift later and later each night. 

This phenomenon can originate from a feedback loop between behavior and the circadian rhythm. Staying up later one night will delay the circadian clock through light exposure, which will tend to move bedtime the next day later. This is compounded if you sleep in later, as you are missing the morning light which can counteract the extra evening light the night before. 

This cycle keeps repeating, slowly driving the bedtime later (for me, this was something like 30 minutes each night). This progression can be curtailed by hitting the circadian wall where the circadian drive to sleep is maximal. This drive, combined with the homeostatic sleep drive which has been building up all day and night, can induce you to finally fall asleep. That doesn’t always happen, though: delay yourself enough, and you might find yourself cycling all the way back to a day schedule. 

  1. I sleep better when I go camping

Finally, one example where you may have experienced the benefits of having healthy circadian rhythms. Many people find that they sleep better when they are camping. This is especially surprising, since this typically means leaving comfy mattresses and other sleep aids behind. Personally, I can fall asleep easily much earlier in the night when I am camping, and– even if I wake several times during the night to roll over– I wake near sunrise feeling much more refreshed than normal. 

A big part of this effect can be traced to the therapeutic effects that camping has on circadian rhythms. These results come from one of my favorite circadian rhythms papers which will be the subject of a future blog post: Stay tuned.

Categories
Technology

Circadian Phase Estimation and Deep Learning

One of the most common questions we get at Arcascope is…

“Can’t you just do circadian phase estimation using machine learning?”

Living in the data age, we have become used to thinking that big data and machine learning can do just about anything. In this post, I will break down some of the unique challenges for circadian phase estimation with an eye towards machine learning techniques.  I’ll also do a brief review of the previous attempts to apply machine learning to this task.