Science Diction Podcast | Sleep

Dr. Amy Manning-Boğ
At the end of another full day, many of us look forward to that moment of peace and quiet and perhaps savoring a glass of your preferred nightly libation. Then you climb into bed and get comfortable. Your thoughts begin to dissipate. Your muscles relax and gradually you drift off into a deep and restorative sleep. Today I’m thrilled to have Dr. Ian Colrain with us. Dr. Colrain is our president and CEO at MRIGlobal and is a recognized leader in sleep research, exploring how sleep is influenced by factors such as menopause, aging, stress, and the nuances of alcohol consumption.

Dr. Colrain’s scientific journey spans over two decades at SRI International and has been enriched by a distinguished academic tenure across the globe from the University of Auckland in New Zealand to Stanford in California with an impressive CV of 350 scientific publications and nearly 12,000 citations. Dr. Colrain’s work has significantly advanced our understanding of sleep. His research traverses the realms of basic applied and translational sciences. Today on the show – sleep – its complexity and the influences of nature and nurture on sleep quality. I’m Amy Manning-Boğ, and this is Science Diction from MRIGlobal.

Dr. Ian Colrain
Sleep is an incredibly important process that involves multiple states and stages, each with different functions for health. It’s regulated by two closely interacting processes. The circadian rhythm comes from the Latin circa dias, about a day, so it’s a rhythm. It’s about 24 hours that increases and then decreases our overall arousal level across a 24-hour period and a homeostatic sleep drive, which increases with prolonged wakefulness and then rapidly decreases once sleep occurs.

It’s important to realize that sleep is not a single homogeneous state. Indeed, the sleep period involves the complex interplay of neurotransmitter systems, physiological processes, and unlike other unconscious states like coma or anesthesia, it’s rapidly reversible. So we can wake up quickly if we need to. And this is clearly important in an evolutionary context, given that our early mammalian ancestors were prey species who were asleep when their reptilian predators were awake. So sleeping soundly, not being able to wake up, not such a good thing.

Dr. Amy Manning-Boğ
I’m honing in on your not a homogeneous state reference. What led to the scientific evidence for this?

Dr. Ian Colrain
So since the 1920s when valve amplifier systems were developed, we’ve been able to measure very small electrical potential differences in the different parts of the body. We’re able to measure brain activity, the EEG or electroencephalograph, very small potential voltage differenced from different parts of the brain and slightly larger ones like the electrical fields produced by the heart, the electrocardiograph or ECG. These signals have been used to define different sleep states and stages based on the changes that we see and the type of activity that we see in different brain and body physiology.

They were codified by a committee in the late 1960s and since then, sleep assessment and laboratory will involve continuous monitoring of the EEG cardioactive activity and other things like eye movements, muscle tone, potentially blood pressure. So these measures reveal that we cycle through two very different states or types of sleep. The first is known as rapid eye movement or REM sleep. During REM sleep, brain activity looks very similar to what we see in wakefulness. The cortex of the brain is essentially very active, almost awake if you like.

All of the major muscles of the body are essentially shut off. And the term rapid eye movement sleep comes from the fact that the eyes move rapidly. Now, it’s been said that if Rechtschaffen and Kales had been measuring heart rate instead of eye movements, they would’ve called it erratic heart rate sleep. If they’d been measuring blood pressure, they would’ve called it wildly fluctuating blood pressure sleep, but nonetheless, rapid eye movements. During these eye movement bursts, other aspects of physiology will also show some activation, so heart rate will increase, blood pressure will change, and you’ll see muscle twitches.

Now I know Amy, you own a cat, so you will have seen this and you’ll be able to impress your children and friends by diagnosing when your cat is in REM sleep because cats go to sleep curled up tight in a ball, but at some point they’ll stretch out, and if you went and sort of picked up their leg, then it would flop straight down, so they’re stretched out and floppy and you’ll see little twitches on the paws.

I would do this with your cat, not your neighbor’s Rottweiler. Nonetheless, it’s very easy to see this in many animals. We think that REM sleep is associated with dreaming, well we know it’s associated with dreaming. We think that now that non-REM sleep might also have some dreams in it. And there are some really good studies that indicate that the overall loss of muscle activity is probably a protection against acting out dreams.

So if you do animal experiments to stop the muscle deactivation, you’ll see the animal running around its cage chasing things, obviously acting out what they’re dreaming about. This can lead to problems if you don’t have this. REM behavior disorder is a sleep disorder that’s often in the news. This is where people will move violently. They’ll punch, they’ll kick, they’ll jump out of bed, they’ll scream, they’ll shout because they are acting in a terrified way, they’re having a nightmare, and they don’t have that inhibition. And patients have been known to wake up with frostbite having left their bed and gone barefoot into the snow all whilst under sleep and dreaming.

Dr. Amy Manning-Boğ
Incredible.

Dr. Ian Colrain
Now, unfortunately, scientists aren’t always very creative when they come up with names for things. So we’ve talked about REM sleep. The other different type of sleep is non-REM sleep.

Dr. Amy Manning-Boğ
Shocking.

Dr. Ian Colrain
Shocking. It’s altogether a more physiologically stable state, but with different depths, usually determined by how far the brain activity is away from the awake pattern. So again, with great imagination, these were initially named stages 1, 2, 3, and 4. But really this criteria for the differences in the different stages were somewhat arbitrary. And it’s now typical to talk about light sleep and deep sleep, light sleep and slow wave sleep, where light sleep is where the brain is in a state that’s closer to wakefulness and deep sleep is further away and it’s a little harder to wake from deep sleep than light sleep.

Dr. Amy Manning-Boğ
Ian, what you’re describing sounds more to me like a whole-body phenomenon, not just a brain phenomenon.

Dr. Ian Colrain
Yeah, I mean, it could be argued that the decade of the brain that we had in the nineties with a lot of funding and neuroscience was great for neuroscience research, but not so good for sleep research because it focused everything on the brain. Sleep really is a whole-body phenomenon and critically important for health maintenance. All sorts of changes occur in the body down to the level of individual cells.

Dr. Amy Manning-Boğ
Oh, please elaborate on this.

Dr. Ian Colrain
So we call sleep an anabolic state, and you’ve heard of an anabolic steroid, bad things, sleep is a good anabolic state. Complex molecules needed for life, such as proteins are synthesized during sleep, they’re synthesized from smaller molecules like amino acids going to proteins. Energy is stored in cells. Sleep also provides a cardiovascular holiday with both the heart rate and blood pressure decreasing during sleep.

And really importantly, it supports immune function and promotes host defense against inflammation and infection. Everybody’s had the experience of when you’ve got the flu, what you want to do is sleep. What your body is telling you need is sleep, and if you get the sleep, you’ll help your body heal itself.

Dr. Amy Manning-Boğ
And if you’re sleep deprived?

Dr. Ian Colrain
Not so good. So one of my favorite studies came out of Carnegie Mellon in 2009, and the researchers somehow managed to get 150 healthy adults to volunteer for this. They monitored their sleep carefully for two weeks before the experiment. And on the day of the experiment, they came in and they had rhinovirus, the virus for the common cold, dropped into their nose. So there’s no mistaking the fact that they’ve been absolutely critically exposed to the virus that gives you the common cold.

Not everybody actually showed seroconversion of the virus and not everybody got the cold symptoms, and they’re able to show that people reporting less than seven hours of sleep in the two weeks leading up to the exposure were nearly three times more likely to develop a cold than those who had more than eight hours of sleep.

And those who slept well based on their estimates of how often they woke up during the night and versus how stable their sleep was, those who slept well were five and a half times less likely to develop a cold than those who slept poorly. So in this case, proactively, sleep was protective of you getting a disease when you were absolutely definitely exposed to the virus.

Dr. Amy Manning-Boğ
Remarkable study. How does sleep evolve through our lives? As you know, being this long in the tooth, I have a vested interest in this answer.

Dr. Ian Colrain
Yeah, sleep patterns and what we call the architecture of sleep, the way it’s put together undergoes significant changes as we age. In utero and as very young inference, sleep is almost exclusively REM sleep. And then non-REM sleep kicks in, starts to appear at around three months.

The really deep sleep, the slow wave sleep that is very common in childhood starts to diminish dramatically with puberty over a three- or four-year period. In puberty, you can lose 20 percent of your deep sleep. And we think this has got to do with the brain undergoing dramatic pruning of connections between neurons. You start off with lots of neurons, lots of connections between them, lots of synapses.

The brain is incredibly plastic, it’s capable of learning lots of different things, but it’s also metabolically very expensive. So given that the skull is in a fixed volume, the head’s not going to be able to grow. The brain’s not going to be able to grow. You have to prune back the number of connections and it’s basically a use it or lose it phenomenon. So as these connections diminish, so does this really deep sleep.

Interestingly, the process starts and ends earlier in young women than in young men, again, relating to sex differences in brain development. Young women mature faster and develop things like good judgment and executive function and fully adult formed prefrontal cortex earlier than men. Makes a lot of sense when you view people’s behavior.

There’s an intriguing change in the timing of sleep during adolescence as well. And we really don’t know why this happens. Lots of studies are now supporting this that teenagers are essentially socially jet lagged by two hours.

So midnight for them is like 10 p.m. for us. So when your teenager wants to lie in bed, not get out of bed in the morning, wants to stay up later, it is not because they’re being difficult or lazy, although it could be that they’re difficult and lazy, but that’s not the reason. They’re obeying the circadian rhythm signals that they’re getting.

Now, unfortunately, this delay coincides with starting high school, which at least in the U.S. starts way too early. And there are good data showing that all of this combines to have many teenagers progressively sleep deprived over the school week and then they do their catch-up sleep on the weekend.

There are some studies indicating that by the end of the school week, their driving behavior and so on is if they had a 0.08 blood alcohol level just based on sleep deprivation. So you add being a new and inexperienced driver to having to get up really early in the morning having not been able to get to sleep until late at night and the sleep deprivation over the week, and you can end up with really dangerous situations.

Another one of my favorite studies came out of the University of Kentucky, Bob Phillips’ lab. The authors analyzed motor vehicle accidents in a single school district county, and they looked at motor vehicle accidents for two years before and two years after the district delayed high school start times by one hour.

What they found was the kids on average slept another 50 minutes a night. Okay. So almost all of those hours of added sleep and the crash rates for teen drivers dropped 16.5%, whereas the teen crash rates for the rest of the state increased by 8% over the same time period.

Dr. Amy Manning-Boğ
So a 25% difference between the two cohorts. Yeah, incredible.

Dr. Ian Colrain
Based on one hour of extra sleep time available with 50 minutes of extra sleep.

Dr. Amy Manning-Boğ
These are remarkable stats, Ian, and it’s a little scary that teens demonstrate this shift or social jet lag effect as you call it. Ian, one area of your research is focused on the intersection of alcohol use disorder and sleep, what drew you to this area of study?

Dr. Ian Colrain
I had really good luck to start working with two of the top scientists in the neuroscience of alcoholism, Dr. Edie Sullivan and Dr. Dolf Pfefferbaum. It’s a joint SRI International Stanford Research Program. And they were doing a lot of work using magnetic resonance imaging of the brain to look at brain structure and brain functional changes in people with alcohol use disorder.

And what they were showing was really quite interesting that alcoholism was really accelerated brain aging. So the normal changes you would see with old age in control subject were being shown in people with alcohol use disorder in their forties and fifties. And at that time I was looking at sleep in normal aging.

So I had the opportunity working with Dolf and Edie to see whether or not the changes in sleep in alcoholics are also showing accelerated aging, which they are, and whether the changes in sleep are associated with the changes in brain structure revealed by MRI. And also that is truly the case.

Dr. Amy Manning-Boğ
Wow. Because there’s this long-standing belief that alcohol serves as a sleep aid and it’s a practice dating back thousands of years.

Dr. Ian Colrain
Yeah, it’s not a modern idea. There’s records showing its use as a sleep enhancer. Going back to the ancient Greeks 6,000 years ago, there’s some lines from a play talking about what one drink will do, what two drinks will do, and three will put you to sleep. So alcohol was recognized as a sedative in ancient civilizations and it has been used throughout history as a means to facilitate sleep. But despite all that contemporary research highlights that alcohol really has a detrimental effect on sleep architecture and sleep quality and challenge this whole notion of its ability to aid sleep.

Dr. Amy Manning-Boğ
Is it really that pronounced on brain sleep architecture and function?

Dr. Ian Colrain
Yeah, so alcohol is a sedative, so it’ll put you to sleep, make you unconscious. And it does seem to show some increases in deep sleep early in the night, but then it reduces REM sleep and in the second half of the night in particular, it’s going to increase sleep fragmentation.

So you’ll just be waking up a lot more. And these effects can exacerbate existing sleep problems and foster a dependence on alcohol as a sleep aid, creating a vicious cycle. So work done in my old lab at SRI with my colleagues, Fiona Baker and Max deZambotti also shows that even moderate blood alcohol levels prior to sleep, so you just have a couple of drinks before you go to sleep, will lead to elevations in heart rate – I’m talking eight 10 beats a minute – that will last the entire night, even when alcohol has been fully metabolized. So again, no cardiovascular holiday.

We also found changes in other cardiac measures and blood pressure. Alcohol also worsens sleep apnea, as it acts as a muscle relaxant. Even non apnea sufferers are more likely to snore after drinking. So even if it’s not impacting their sleep, it will impact their bed partner quite severely, and I’m sure many of us have experienced that.

Dr. Amy Manning-Boğ
The journey into alcohol use disorder, or AUD, is marked by escalating patterns of binge and heavy drinking. This path can trigger a series of adverse consequences over time, deeply affecting one’s sleep and overall health.

Dr. Ian Colrain
It’s important to understand that AUD, like other addictions, is a disease. It’s a nasty disease and it’s hard to treat. It can be chronic. It’s diagnosed using three criteria, craving alcohol or a strong desire or urge to use alcohol, recurrent alcohol use, resulting in a failure to fulfill your role or obligations at work, school, or home.

So you’ll keep drinking even when you lose your job, even when you’re not looking after your kids and so on. And continued alcohol use despite having persistent or recurrent social or interpersonal problems that are caused or exacerbated by alcohol. So it’s basically a compulsion, it’s an addiction, you just keep using it.

One model of AUD proposed by the current director of the National Institute of Alcohol Abuse and Alcoholism, Dr. George Koob, references three distinct phases in the development of AUD. An initial binge drinking intoxication phase with excessive drinking that leads to tolerance and dependence.

Then if you stop, a withdrawal or negative affect phase is associated with not being able to use the alcohol, physical, physiological withdrawal and so on. And then a preoccupation or anticipation phase where you are over the initial effects of withdrawal, but you still are constantly thinking about your next drink.

Now George is one of the world’s top neuroscientists, and he developed this model based on his knowledge of how different parts of the brain and different neurotransmitters that are impacted by alcoholism are involved in these different phases so that this initial binge and intoxication stage is associated with excessive engagement of reward circuitry in the brain.

The negative emotional state is associated with activation of some of the brain’s emotional regulation centers, such as the amygdala. And the extended preoccupation anticipation stage may be associated with damage to essentially dysregulation of the frontal cortex of the brain.

And his work and others have been able to identify multiple neurotransmitter systems that are involved in these different brain areas and processes such as gaba, glutamate, endogenous opioids, and dopamine. Though these neurotransmitters together with acetylcholine and other neuropeptides are also intrinsically involved in sleep regulation.

So for example, the decreased time to fall asleep with high blood alcohol levels is almost certainly due to alcohol’s activation of gabaergic systems that both promote non-REM sleep and inhibit REM sleep. So dysregulation of these neurotransmitter systems that lead to dependence and increased tolerance can be very long lasting and are likely to be the cause of the persistent insomnia that we see with abstinence. And that can last for many months and can be a trigger for relapse.

Dr. Amy Manning-Boğ
So then as a takeaway message, alcohol is a good idea for a sleep aid or not so much?

Dr. Ian Colrain
Unfortunately. No. And you’ve known me a long time. This is really hard for me, I like my wines, I like my single malts, but it’s now really clear that there are absolutely no health benefit associated with drinking even in moderation and certainly no benefits to how you sleep. Hot milk’s a better idea.