Can Enhancing Slow Wave Sleep Boost Your Brain Function? Podcast with Kristine Wilckens

It is well established that lack of sleep impairs brain performance. Of course, you don’t need to see any studies to know that this is true. Every single one of us has experienced this firsthand. With respect to mental performance, however, it’s not merely the duration of sleep that matters. Quality of sleep, and particularly how much time you spend in deep sleep, or slow wave sleep, seems critical, too. Here’s why.

Slow wave sleep seems to be a uniquely restorative state. For instance, growth hormone secretion is highest during this sleep phase, which helps facilitate tissue repair and muscle remodeling. Additionally, slow wave sleep appears to be crucial in the processes of learning and memory storage.

As we discussed previously in our interview with Bryce Mander, sleep architecture changes with age. Reduction in slow wave sleep, in fact, is one of the most notable alterations. One study of 149 healthy men found that from early adulthood to midlife, the percentage of slow wave sleep dropped from 19% to 3%, with a corresponding increase in lighter stages of sleep. Unsurprisingly, growth hormone secretion also decreases by about 75%.

It is thought that sleep quality plays a key role in cognitive function. Interestingly, it has been shown that both younger and older adults perform better in tests of memory and cognition when they get more of this deep restorative sleep. So, could altering sleep structure – particularly by enhancing slow wave sleep – improve brain function?

That brings me to my guest this week.

In this episode of humanOS Radio, I speak with Kristine Wilckens, Assistant Professor in the Sleep and Chronobiology Center in the Department of Psychiatry at the University of Pittsburgh. Her research focuses on neural mechanisms that link sleep to cognition, and ways that sleep can be altered to enhance cognitive function.

As you can imagine, she is uniquely qualified to speak on specific methods to improve sleep quality, and how these alterations in sleep architecture can affect how your brain works.

Broadly speaking, activities that increase brain energy consumption during the day seem to correspond to a rebound decrease in metabolic rate at night. This, in turn, results in an increase in slow wave activity during sleep.

So what sorts of activities are we talking about here? Many of them are things that you can literally do right now.

Research suggests that exposure to heat activates warm-sensitive neurons in the hypothalamus, which promote slow wave sleep in response to the increased body temperature. This can be achieved actively, like through intense exercise, or passively, via warm baths or saunas.

Mental activity may also augment slow wave sleep. It has been reported that the process of learning, like in various cognitive training tasks, produces changes in non-REM sleep. This relationship is obviously bidirectional, since improvements in cognition also depend upon slow wave sleep.

Finally, meditation has been demonstrated to increase slow wave sleep. Meditation practice is associated with increases in theta activity (measured via EEG), which is related to memory encoding and increased slow wave activity in subsequent sleep.

There are some other compelling methods, like transcranial stimulation and even exposure to certain types of sounds and scents during sleep, which we discuss in the podcast.

This area of research is obviously immediately relevant for preserving cognitive function and fighting neurodegeneration in an aging population. But it should actually be enticing for most of us, since so much of our work and daily responsibilities are tied to our thought processes and our capacity to learn. And besides, who doesn’t want a better brain?

To learn more about science-based techniques to enhance slow wave activity and make your brain work better, please check out the interview below!

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Dan prepared for and conducted the interview, Greg helped prepare questions, Ginny wrote the blog post, and Kristine did all the hard work in the lab!

Kristine Wilckens - 00:06: There's definitely a lot of evidence to support that anything that is stimulating and exciting the brain during the day leads to a rebound decrease in metabolic rate, showing this increase in slow wave activity at night.

Kendall Kendrick - 00:24: Human OS. Learn, master, achieve.

Dan Pardi - 00:33: Welcome back to Human OS radio everyone. Today I have with me Kristine Wilkins, assistant professor in the Sleep and Chronobiology Center in the Department of Psychiatry at the University of Pittsburgh. Welcome to the show, Kristine.

Kristine Wilckens - 00:44: Thanks, happy to be here.

Dan Pardi - 00:46: I came across a review paper that you were the first author on in the Cell Press Journal, Trends in Neuroscience, entitled Slow Wave Activity Enhancement to Improve Cognition. Let's first discuss what the term cognition encompasses.

Kristine Wilckens - 00:57: Sure. Cognition can refer to a variety of things. Basically, any kind of thinking. What we're talking about in this paper, it's mostly about cognitive processes that involve higher order thinking, like what we call executive functions which are goal-driven processes. If you really wanna concentrate on something, focused attention as well as memory performance, that would be distinct from emotion cognitions about emotions and those sorts of processes. What we focused on in this paper is more neutral cognitive processes. But you could just broadly think of it as thinking.

Dan Pardi - 01:43: So much of what is required of us today has a lot to do with how well are brain is working. This idea to possibly enhance aspects of sleep that then lead to enhanced cognition is very exciting. Before we move on to the enhancement, talk a little bit about how sleep is structured.

Kristine Wilckens - 01:58: When you're first falling asleep, you're in stage one. You progressively get into deeper and deeper sleep, and we call the next stage of sleep stage two sleep. That's when we know the person is actually asleep. It's characterized by specific features that you see in the person's electroencephalogram, their EEG. What those features are are sleep spindles which are faster waves as well as K complexes which is kind of a fast up-and-down wave, just one big up and down. Then as you progress further and further into deeper sleep, then the EEG slows down more and more to the point that you are seeing what we call slow waves. They're about less than 4 hertz, so they're very slow ... in the order of seconds ... and that's what characterizes the deepest stage of sleep.

02:55: After you get through a cycle of stage one to three non-rapid eye movement sleep, you then go into rapid eye movement sleep, also called REM sleep, and that's when we have dreaming.

Dan Pardi - 03:10: What is slow wave activity and what do you think drives this activity?

Kristine Wilckens - 03:12: It's a lot of a decrease in brain activity, particularly in frontal brain regions. If you measure metabolic rate in the brain during sleep, you see a dramatic decrease in metabolic activity that is happening mostly during slow wave sleep. Contrast that to wakefulness when there's a lot of faster EEG activity. There's a lot of different things going on. It's more synchronized during slow wave sleep, so you have a lot of neurons working in synchrony all doing the same thing, all firing simultaneously in this slow fashion. It involves two states. There's the down state and there's the up state. The down state involves inhibition of neural activity. All that inhibition then leads to a rebound increase, a spike, in activity which is very brief. You call that the up state. Then it goes back to the down state. That's what ultimately leads to this wave that looks like a slow wave where it's going up and down very slowly. That's what characterizes slow wave sleep.

Dan Pardi - 04:28: Talk about the coordination between higher metabolic rate during daytime activity with thinking, and then how that will promote the slow wave activity that you see during this stage of sleep.

Kristine Wilckens - 04:38: That is the main premise of this paper that we had where we talked about what your brain is doing during the day and how you can manipulate that in order to see an enhancement of slow wave activity during sleep. There are variety of ways that you can increase the ... for your example that you gave ... metabolic activity in the brain during wakefulness. We have a variety of techniques that we reviewed where you're basically enhancing energy consumption in the brain during the day. Cognitive activity is one. Meditation is one. There's also brain stimulation techniques that are done in the lab, and then also exercise which tends to increase body heat as well as brain heat. These techniques have all been shown in some form or another to lead to enhancement of slow wave activity.

05:42: It's kind of like the higher up you go during day, the more down you're going to be at night in terms of your metabolic rate in your brain.

Dan Pardi - 05:52: That's a very interesting thought. If you use your brain intensely in this variety of ways: physical activity, thinking, meditation, all of those things will be reflected in the type of sleep that you get at night.

Kristine Wilckens - 06:04: That is right. There's definitely a lot of evidence to support that anything that is stimulating and exciting the brain during the day leads to a rebound decrease in metabolic rate showing this increase in slow wave activity at night.

Dan Pardi - 06:20: Because you're using energy, particularly in this prefrontal cortex, during the day, is that part of brain really driving the activity of the slow waves?

Kristine Wilckens - 06:29: That's an interesting question. There's this idea of local sleep that Tononi and colleagues have proposed where the more that you use a particular brain region, that you'll see localized increases in slow wave sleep over that particular brain region. It's not just the prefrontal cortex that we see slow wave sleep in general. It's predominately over the prefrontal cortex, because that's an area that's get used a lot during the day, but there is also evidence that if you do, say, a visuospatial task is one task that they've used to demonstrate this. A visuospatial task where you have to track the spatial location of something on the computer screen, and that really depends on the parietal cortex. What they found is that they demonstrated an increase in slow wave activity over the parietal region where this task mostly depends on.

Dan Pardi - 07:32: One function of slow wave activity has been proposed to be sort of a file transfer mechanism. Memories encoded during the day are shipped from the short term storage in hippocampus to the longterm site in the neocortex. Can you describe what sleep spindles and sharp wave ripples are, which you mentioned the spindles earlier, as well as the role of low wave activity in coordinating this transfer process?

Kristine Wilckens - 07:50: It seems as though the coordination of those three sleep features are what's critical for the consolidation of memories that occurs with slow wave sleep. Slow waves are very global. They are primarily over the prefrontal cortex, whereas spindles are thalamocortical. They're basically a loop that occurs between the cortex and the thalamus. Those occur at 12 to 16 hertz. There's faster, sharp wave ripples that mostly are able to see in an animal by inserting an electrode into the hippocampus. There's a little bit of evidence that we can see them in humans, but that's a work in progress right now. The sharp wave ripples originating from the hippocampus are basically thought to be like the information processing units that carry the memory information. Then the spindle is what helps to transfer that information from the hippocampus, so there's limited resources in the hippocampus. If you stored all of your memories in your hippocampus, there would be no room for new memories. You have to spread your memories out to other parts of your brain over time.

09:11: The spindle is what is supposed to facilitate the spreading of this information over other parts of the brain so that it can free up resources of the hippocampus. This is what is occurring primarily during slow wave activity.

Dan Pardi - 09:29: The hippocampus is almost like a weigh station for new memories, that the stimulation that takes place during the day and at night, in accordance with these three characteristic EEG features, you then see the transfer of those memories out of the hippocampus and into the neocortex.

Kristine Wilckens - 09:42: Correct.

Dan Pardi - 09:43: Slow wave activity has also been important for something called synaptic scaling. What is this, and what are its effects?

Kristine Wilckens - 09:49: There's a lot of evidence that during wakefulness, you're building a lot of connections between neurons in the brain by having experiences, new connections in your brain are made. What happens during sleep is sleep's ... One of the main roles is to basically say, "Okay, a lot of these connections were made. We don't need these anymore, and we're going to downscale those connections." Getting rid of those connections is one of the main cognitive functions of sleep, but there's a little bit of debate about this scaling basically promotes memory consolidation. By one view, which is from Giulio Tononi's group, there's no enhancement of connections during sleep. It's all decreasing connections. Basically, you are honing what connections are important by getting rid of irrelevant connections.

10:49: In contrast, a more active view would say that, "Okay, there's down scaling of irrelevant connections, but then maybe there's also up scaling of relevant connections during sleep." Basically, if-

11:02: ... feeling of relevant connections during sleep. Basically, if during sleep some of our memories are being reactivated, then those connections that represent those memories could actually be strengthened during sleep.

Dan Pardi - 11:15: It's interesting that when you learn the sign of a good memory is actually forgetting things that might cloud the focus on things that are more important.

Kristine Wilckens - 11:23: Right. There's this interesting idea that certain information gets tagged as relevant based on emotion, or motivation, importance to the person. That slow-wave activity tracks that tagging and is able to enhance slow-wave activity particularly for things that are most relevant to the organism.

Dan Pardi - 11:49: Let's move on to enhancement of slow-wave activity. Who do you think might benefit most from interventions that increase this type of activity? Is this something that potentially anyone could benefit from? Is it just in the elderly, or people that have neurodegenerative disease. What do you think is the scope of potential technologies in this field?

Kristine Wilckens - 12:06: I think that there a variety of populations, some more obvious than others. Older adults, for instance, have a lot less slow-wave activity than young adults. In adolescence, you have a ton of slow-wave sleep. Then as you get older from there, it basically declines. There are some older adults who maintain somewhat higher levels of slow-wave activity and some who do not. That's an important question, figuring out what leads to that, number one, but also can we enhance it individuals who have particularly reduced slow-wave activity, or even just a healthy, older adult?

12:51: I think that there is sufficient evidence to suggest that enhancing slow-wave activity even if you're not part of a patient population that that's definitely has beneficial effects, a huge literature on memory consolidation and sleep is done in young adults, demonstrating that increases in slow-wave activity and coupling with spindles is what leads to improved memory performance over one night, for instance. There's not a lot of research in the long run on enhancing slow-wave activity. That's definitely something that people are getting more and more excited about because it could be so relevant for people who have basic cognitive aging, but also people who have cognitive impairments or at a later stage of neurodegeneration. We're doing a lot of research in mild cognitive impairment right now to see if enhancements of slow-wave activity can improve executive functions, so this goal driven processing, as well as memory performance. Then also schizophrenia is an example of a population where this kind of research can be critical because they tend to have lower slow-wave activity as well in addition to well-documented cognitive issues. I think that the aging population and certain mental health groups, particularly those with schizophrenia could benefit most from this.

Dan Pardi - 14:27: We talked a little bit earlier about things that at least track [inaudible 00:14:30] increase in slow-wave activity, so things like exercise and mentally challenging tasks, also things like sex and heating of the brain's [inaudible 00:14:38] sensitive neurons in the hypothalamus. A lot of these things seem to track with markers of energy usage, a lot of immune chemicals like Interleukin 1 Beta and TNF Alpha or activation of parts of the hypothalamus, even hormonal changes too. We talked about those, and now the novel ways of enhancing, let's talk about some of those. This is things like transcranial stimulation, olfactory stimulation, vestibular stimulation. Can you speak a little bit about each of these and their relative merits and shortcomings from what we know about them now?

Kristine Wilckens - 15:07: Sure. First of all, vestibular stimulation I would group in with all of the other more natural slow-wave sleep enhancing techniques. That's just rocking, like having a bed that's rocking. People always talk about how you can help a baby fall asleep by rocking them. That's probably tapping into these same mechanisms. Ultimately, what the mechanism is is in training the brain to fire within this low frequency. By slowing rocking an individual, their brain gets entrained to that rhythm. You end up with this global, synchronous, low-frequency activity that characterizes slow waves. That can help a person fall asleep. Some evidence shows that it can also enhance the amount of slow-wave activity.

16:03: These transcranial stimulation techniques that you mentioned work through that same mechanism of trying to slow the brain down. There's transcranial magnetic stimulation, for instance, which creates a magnetic field. Then you can stimulate the brain at the frequency that you want that brain region to be excited at. If you stimulate the brain, you know, let's say a part of the prefrontal cortex, stimulate that at less than one hertz, a very slow frequency, then you can make the brain have slow waves, if you do this during sleep and if it's at an optimal time for slow waves to be generated. It is important that it is during sleep, and it's at this optimal time. They don't tend to show that you can just have an awake person and start stimulating them at one hertz, and then they're asleep in deep sleep. You can basically enhance the slow waves that are already likely to be generated naturally. That's one approach.

17:13: Then also on the flip side of that, analogous to exercise, I think, but in a brain stimulation way is basically to use higher frequency brain stimulation during wakefulness. That, again, increases energy consumption in the brain, which ultimately your brain naturally rebounds from by increasing slow-wave activity.

Dan Pardi - 17:40: [inaudible 00:17:40] that is playing different frequency ranges. Has that type of technique been utilized to try to [crosstalk 00:17:46]?

Kristine Wilckens - 17:46: Yeah, that's interesting. You're saying auditory stimulation during wakefulness, if it's higher frequency. Is that what you're saying?

Dan Pardi - 17:57: Yeah.

Kristine Wilckens - 17:57: One approach that has been used that's similar to that is visual stimulation like high-frequency visual stimulation during wakefulness. There are some studies on that. They tend to look more at insomnia and falling asleep, so whether that decreases your sleep latency, how long it takes you to fall asleep. Those do show positive results, again in line with this idea that if you can really excite the brain during wakefulness, that ultimately leads to this cascade where the brain wants to recover from all of that excitement, if you will. Then that is what ultimately is manifested with the slow-wave activity.

Dan Pardi - 18:46: Some people have suggested that slow-wave activity is actually epiphenomenal. That's to say that while slow-wave activity coincides with this period where these different cognitive enhancing activities are taking place, it doesn't play a causal role in coordinating the deep sleep. What are your thoughts on this?

Kristine Wilckens - 19:01: I think that that is completely reasonable, number one. I think that there's more likely a bidirectional relationship, but what definitely makes sense is that slow waves are generated by the prefrontal cortex. Someone whose prefrontal cortex is degenerating is just not going to be able to generate high amplitude, slow-wave activity. By the same means, they are not going to be able to perform cognitive tasks to the same extent as somebody whose prefrontal cortex is not degenerating. I think that it is totally reasonable to think that this relationship is bidirectional. It would be nice, I think, if it is the case that slow-wave activity can be modified, and that that could have a positive influence on cognition because sleep is modifiable, and it's hard to change someone's brain. I think that it would be great if we could find ways to modify slow-wave activity that can be useful in the long run, but I think it's definitely the case that somebody who ... For example, someone with Alzheimer's disease who has a lot of neurodegeneration. They have not a lot of slow wave activity either. I think that it's very much reasonable to think that it goes in the direction of brain is degenerating, and that's affecting the sleep.

Dan Pardi - 20:36: The slow-wave activity perhaps might be permissive and necessary in order to allow for the background processes to occur. If you can't get into that permissive environment, that could then inhibit those memory forming transfer processes to occur. Enhancing a condition that you're already getting an adequate amount of might not see a lot of additional enhancement. It could really just be of clinical benefit for those that are missing that state versus enhancement for those who are getting an adequate degree through proper lifestyle stimulation.

Kristine Wilckens - 21:07: I think there is enough evidence at least in the short-term that if we enhance slow waves, that that does enhance memory just whether is the long run, so cross-sectionally, for instance. If you relate slow-wave activity in one individual to their cognitive performance or their memory performance, there's definitely a lot of positive studies showing that people who tend to have higher slow-wave activity tend to have better cognitive performance, better memory performance, but it's not always the case. Definitely, in terms of understanding the long-term consequences of slow-wave sleep enhancement, that very much remains to be seen.

Dan Pardi - 21:54: If you do try to optimize for slow-wave sleep enhancement, is there some sort of competitive inhibition of other processes that are important in different ways?

22:03: ... addition of other processes that are important in different ways. You're optimizing for memory, but you're also then potentially having a down stream negative consequence of that enhancement. Do you think that that is a real possibility?

Kristine Wilckens 22:12: Are you saying that by basically interfering during somebody's sleep by stimulating their brain or playing tones or something like that during their sleep?

Dan Pardi - 22:23: Exactly. I think you can do that in phase lock fashion that might have greater-

Kristine Wilckens - 22:28: Right, I think that that is an interesting point. There's a lot of interest in these techniques that you can use during sleep to be able to deepen your sleep, acoustic stimulation in particular. There's so much research on acoustic stimulation. Giulio Tononi, there's a product to do this to increase slow wave sleep through acoustic stimulation. There's a lot of interest in that, and there is some interest as well in the brain stimulation techniques during sleep and certainly scents definitely a promising avenue. Having lavender oil, for instance. There are very few studies, but to my knowledge they're all positive effects. I haven't seen too much conflicting evidence for presentation of lavender during sleep, but whether that is actually good to have all night every night. Same thing for the other techniques, whether that is really in the long run going to be good for your sleep. Is a person going to be dependent on that either psychologically or physiologically?

23:44: This is why I think that some of these wake techniques where you have a natural rebound in slow wave activity such as exercise, sexual activity, cognitive activity ... although I would say exercise probably has the most robust effects. Those types of activities, I think, are very promising for long term effects. Granted, they take more work on the part of the individual and more motivation, but I think that the obvious benefit of them is that there is absolutely no interference at night time in order to enhance the slow wave.

24:25: One thing that we're working on right now is doing brain stimulation during wakefulness. In that case, it doesn't take as much motivation on the part of the patient or participant, but again, enhancing slow wave activity but without having to go in and interfere at night.

Dan Pardi - 24:43: I'm always interested in the techniques that fully leverage lifestyle behaviors first, but it is also interesting to think about the environment. Can you play pink noise in the background during sleep, and is that going to be only positive?

Kristine Wilckens - 24:55: Yeah, I totally agree. I find the idea of enhancing your lifestyle in order to enhance sleep and ultimately other aspects of your life to be so interesting. I mean, warm baths is one of these techniques that I think is just so fun to think of it as something that enhances your sleep. Nobody has really looked at it ... at least no publications have come out with warm baths and how that affects your sleep to ultimately improve your cognitive performance, but there's a lot of evidence that taking a warm bath at night enhances slow wave sleep. Those kind of things are really intriguing and there is evidence that if you do this closer to bed time that it is more likely to enhance deep sleep.

25:46: The pink noise thing is interesting because it's in contrast to white noise. It has more low frequency noise, and that is ultimately low frequency is what we're trying to entrain the brain to do when we want to enhance slow wave activity.

26:03: Interestingly though, Phyllis Zee who has published on this in particular using pink noise, she has said that she doesn't think that it needs to be pink noise, per se, but any noise as long as it's phase locked to the upstate of the slow wave. Basically, you want to enhance neural excitement at the moment that the slow wave is at its tallest. You don't want it at any old time. That's not going to enhance your slow wave. That is kind of intriguing. I think that there's definitely going to be a lot of interest in whether you could just play pink noise while you're sleeping and get similar benefits. As of now, it seems like the time locking and real time measurement of EEG to know when you're slow wave upstate is happening and then have the pink noise aligned with that. It's a lot more complicated than just getting a noise machine, at least as far as we know in terms of what leads to actual benefits.

Dan Pardi - 27:08: I think about the concept of interventional impact where if you do get some benefit by playing pink noise ambiently in your room environment, and your brain entrains to that frequency and it augments either the amplitude or time spent in slow wave sleep, and that leads to memory enhancement without any sort of diminution of other important EEG brain activities like in REM sleep. Cool, that's great. If you do get an enhancement beyond that by phase locking it and playing that pink noise signal at the exact right time but you do need to wear, let's say, a headband that is going to cause possibly more friction, a lot fewer people can do it, how much greater is the benefit with the more sophisticated device and can way more people actually get the benefit of just having the pink noise in the background?

Kristine Wilckens - 27:51: Yeah, and I don't think we have an answer to that question yet, because, in general, the studies have a control condition that is basically using similar amount of some other kind of noise or interference. How these acoustic stimulation techniques compare to just letting the person sleep naturally has been less investigated, and mainly because you want to have a tight experimental control, but now people are interested, "Can I actually use this at my home, and will it actually be good for me?" We have less of an understanding about that right now.

Dan Pardi - 28:31: Daniel Gardner who gave a TED talk about slow wave sleep enhancement has sonic sound. It can play pink noise in the background. There's even channels like YouTube that have eight hours of pink noise, but sometimes those can get interrupted by commercials. If we don't have to use an expensive device and wear it at night, we can get all the benefit from doing the right things during the day that's always what I would opt for, but I love the fact that these technologies are being generated so that people that are out of the window of being able to utilize lifestyle techniques to get all the benefit could somehow get rescued. That is exciting to me.

Kristine Wilckens - 29:06: Yes, getting on a virtuous cycle of exercising benefiting your sleep, that sleep allowing you to be more recovered, and then being able to exercise, etc.

Dan Pardi - 29:19: Do you plan to do more work in this area going forward?

Kristine Wilckens - 29:22: Definitely. One thing that we are funded to do is to look at brain stimulation during wakefulness in people with cognitive impairments and ultimately look at slow wave activity as a mechanism of cognitive improvement. We are very interested in Alzheimer's disease and starting to look at how slow wave sleep is involved in clearance of amyloid which is a marker of Alzheimer's disease in the brain. Yes, things are getting very exciting in that regard, because there's a lot of interesting animal work showing the role of sleep in Alzheimer's disease markers. It's just a very intriguing idea and something that we definitely plan to pursue. We also have some data that is just accepted but is showing a role of sleep in amyloid and cognitive performance as well. Definitely doing a lot of this work moving forward.

Dan Pardi - 30:27: Kristine, thank you so much for your time. I've been fascinated by this line of work for a while, and this gave me a great excuse to look into it more deeply.

Kristine Wilckens -30:33: Yeah, thank you for these great questions. This was fun, and I'm very happy to be involved.

Kendall Kendrick - 30:41: Thanks for listening, and come visit us soon at humanOS.me.