In this episode, Giovanni Santostasi discusses the relationship between slow-wave sleep and memory consolidation. His team has developed a technology that uses sound during sleep to amplify brain waves. Their research has demonstrated a 400% increase in memory consolidation during sleep using this sleep tech.

In This Episode We Discuss:

• How slow-wave sleep impacts long-term memory
• Healing and regeneration during slow-wave sleep
• Using sound during sleep to amplify brain waves
• Deepwave technology that increases memory consolidation during sleep by 400%

Show Notes:

3:17 overview of brain waves
12:50 delta waves (slow waves) during sleep
23:27 REM and non-REM sleep
28:40 benefits of slow-wave sleep
33:00 anti-aging and sleep
36:51 why binaural beats and isochrones don’t work
45:54 memory consolidation & creativity during sleep
48:45 using sound during sleep to amplify brain waves
57:00 why timing matters when stimulating the brain
1:10:48 phase lock loop algorithm to deliver stimulation
1:12:07 results of study to improve memory by improving waves
1:27:32 target memory reactivation technology and learning during sleep

Mentioned in This Episode:

TED talk - One more reason to get a good night’s sleep
https://www.deepwave.tech

Full Episode Transcript:

Daniel S.: Welcome, everybody, to the Neurohacker Collective podcast, Collective Insights. My name is Daniel Schmachtenberger. I am with the research and development department here at Neurohacker Collective, and we are excited to have Dr. [00:00:30] Giovanni here with us. Giovanni, just so I don't butcher the Italian, will you pronounce your last name for us?

Giovanni S.: Yes, it's Giovanni Santostasi.

Daniel S.: Santostasi. And so you all will get to appreciate a nice Italian accent along with the information today. Giovanni is doing work that I actually think is completely revolutionary, groundbreaking work in the field of neuroscience, and so it was really delighted to have him on, and he's going to be sharing about his work [00:01:00] in biophysics and neuroscience today.

So unlike some of the podcasts where we're sharing information that you can go apply yourself directly, this is really helping you understand things about the brain about neurotech and the future of the field better, so if that's interesting, that's where we'll be going.

His background was in physics and then moved into neurology. He's a research professor at Northwestern University in the Neurology Department, but specifically working in kind of the [00:01:30] biophysics of neurology interface. He actually saw what we were doing with Neurohacker Collective and reached out to me. We did our undergrad in physics at the same university, which is a small private university that, specifically, we both went there to study the intersection of physics and consciousness research, and then both got into neuroscience, so we have a fun connection and have had a lot of really fun dialogs.

He founded a company that is in early stages now called [00:02:00] DeepWave. He's the chief scientist there that is working on the application of the tech that we're going to talk about that has been funded by various military and research institutes, and it has the capacity to create ... If any of the early research ends up being able to be brought to market, really paradigm shifting breakthroughs in sleep, and memory, and learning, and probably a lot of other things, and so that's what we're going to explore today.

[00:02:30] So Giovanni, thank you for being here with us today.

Giovanni S.: My pleasure.

Daniel S.: So your tech works to the ... There's two different parts of the tech, but we're going to start with the phase locked work, and so people need to understand brain waves a bit for this. So when we talk about someone being in delta sleep or an alpha or a theta brain wave pattern, specific frequencies that do specific things, for those who don't understand what this is, can you just give a short overview of [00:03:00] what these brain wave patterns are, what causes them, kind of what they do, and then we'll talk about why there have been technologies that try to drive specific brain waves, why you found that that was not that useful, and what you found instead.

Can you start with just an overview of brain waves?

Giovanni S.: So like everybody knows, the brain is mostly made by these cells that are called neurons. There are some supporting cells as well, but the [00:03:30] main bulk of the brain is made by these cell called neurons, and they communicate both using electrical messages and chemical messages. The electrical messages are coordinated to oscillations, so basically the neurons communicate, and they respond to sensory information from a [inaudible 00:03:58] by activating and [00:04:00] deactivating, we call these in the field polarization and depolarization, [inaudible 00:04:07] polarization.

So usually neurons stays in a negative voltage that is its resting state, and then when it wants to communicate with other neurons, there is what is called a spike. There is a discharge of ions that travel out along the axon that is this long extension of a neuron, [00:04:30] so that reaches out to other neurons, and this electrical activity is coordinated, is oscillated.

So oscillations have characteristic times. They, in the brain, they can go all the way to a fraction of a second, for example, during waking, most of the brain activity happens 10 times a second, 10, 15 times a second.

[00:05:00] So a frequency, what we call a frequency is basically how many oscillations you have per seconds. So in the range of the frequency that we observe with that characteristic of the brain, they go all the way from, let's say, 0 or 0.1, let's say, maybe it takes 10 seconds for an oscillations to happen, all the way to hundreds of oscillation per second. These are hundreds of oscillation per seconds [00:05:30] are called gamma.

So historically, researcher discovered these oscillations using the first rudimentary devices, so basically, the entire field that we ... This field that I'm starting, it's called electroencephalography, basically, we measure these electrical impulses. They are very, very small, so they're, everybody's from [inaudible 00:05:53], right? So we use electrodes with ... We apply on the scalp, [00:06:00] and we measure this electrical activity. It's in the order of a millionth of a volt. So it's very, very, very weak.

And the first evidence that the brain was producing electrical oscillations came about in the '30s, and so people started to name these oscillations with different letters of the alphabet. So the first oscillation [00:06:30] that was discovered was alpha, because if you close your eyes, for example, you see that this very, very dominant frequency that is about 10 oscillation per seconds, so about 10 hertz. And so they called it alpha.

And then, little by little, a researcher discovered other frequencies, so now we have an entire range that we go from the lowest oscillations that go around two or three oscillations, sorry, two or three seconds it takes, [00:07:00] on oscillation, it takes two or three seconds to about half a second, so 0.5 hertz to 4 hertz. This is called delta. Then we have theta from 4 to 8, then we have 8 to 12.

And we are arbitrary. We are not [inaudible 00:07:16], you know, different researchers use a slightly different frequency. But about between eight to 12, but the range is called theta, and sorry ... four [00:07:30] to eight is called theta, eight to 12 is called alpha, and above 12 to about 30 is called beta, and then above 30, we have these high frequency oscillation that is called gamma that is very typical of primates, so just primates now, but animals that are, [inaudible 00:07:53] say, less advanced and evolved in human brains and primate brains, [00:08:00] they don't have almost any gamma at all. And as you go all the way to simpler animals, like lizards, they don't have a match of a higher frequency, like beta, for example. So they are mostly, even when they are awake, they have mostly slow frequencies.

So it seems that there is some kind of ... So the reasons we, in terms of what is the significance of these oscillations, people are starting to give more and [00:08:30] more importance to these oscillations. In fact, there are people, there are some researcher, they are calling it the language of the brain. So the brain encodes information through these oscillations, and so there are some researchers, so there is a beautiful book that is called Riddles of the Brain that I suggest to the podcaster listeners. And it's [00:09:00] explaining that all the different relevant frequencies and why very important. So they seem to be associated to different operations with the brain [inaudible 00:09:11].

So for example, during the day, you see this electrical activity, but it's very, very fast, and non-coordinated. So it's probably different areas of the brain doing the wrong thing, so there is visual information in the back of the head that is processing what [00:09:30] you're seeing, auditory information, and they are coordinated, but they are not super coordinated. And so this is why, for example, the waves are fast, because they are mostly local. So they are frequencies, also.

So there is this idea that a fast wave is going to have a wavelength, right? So a wavelength, if you look at the wave, is the distance between peak to peak, and if you have a really fast waves, you are going [00:10:00] to have a short wavelength. And so that means, in terms of the size of a wave [inaudible 00:10:06] small wave, and so probably something that is produced locally in the brain. If you have a very long wavelength or very long frequency, it's probably a wave that covers the entire size of the brain. And so that, it's a sign of an activity that takes place in a very coordinated fashion over long distances in the brain.

And so [00:10:30] this is very relevant for what we do, for example, because during sleep, one of the measures that we have to determine that somebody falls asleep is that the wavelengths became ... They go from there's a very fast activity that you see during waking and wear out because there is not much coordination, and the waves are very small, as you can see almost with your naked eye. So if you follow the brain waves, so we usually put electrodes all over [00:11:00] the head, but it's enough to have only one single electrode here on the forehead, and you see the activity from that region of the brain. We're going to see as you fall asleep, these waves became bigger and bigger and bigger in size, but also slower. So they go from 10, 15 oscillations a second all the way to one oscillation per seconds.

When you start to see these very large one per second, almost one per second, [00:11:30] oscillations, these activity, we call it slow waves, and is actually the deepest part of sleep. So it's actually something that is relatively easy to observe, even by naked eye, and actually detect with some simple algorithms.

Daniel S.: So for those of you who heard the podcast we did with Dr. Andrew Hill from UCLA a little while ago, [00:12:00] you heard him talking about EEG and specifically using qEEG as a method of actually being able to assess people's ... Certain kinds of psychological, cognitive, and neurological attributes, and then actually be able to use EEG-based neurofeedback to help train the brain.

So and for those who haven't heard it and are interested in this topic, it's a great podcast to go listen more to what different kinds of brainwave patterns in different brain regions during waking state correspond [00:12:30] to. But we're going to go a little bit now into specific brain wave patterns during sleep and what they correspond to.

So you were just mentioning slow wave sleep in the delta range, and you mentioned theta but didn't talk about what it does yet. You want to talk a little bit about the phases of sleep and how they correspond to brain waves and what's happening?

Giovanni S.: Yes. So I have a physics [inaudible 00:12:53], and one of the things that really fascinated me about sleep is that among all the different [00:13:00] neuroscience phenomena, it seems among the most regulated, the most ... The part of neuroscience that seems to have a more specific patterns that can be studied that can be studied, but in a mathematical fashion. So one of the things that we observe is this very nice regularity of the brain activity, the electrical activity of the brain, that seems to have cycles, so what we call [00:13:30] cycles.

Now we're talking about a biological system, so it's not like the mechanical system, which we study in physics, where everything is extremely regular, right? So these cycles are relatively regular. So basically, what you observe, right, is what I describe it for. So as somebody falls asleep, you see an increase in these delta waves, and these, I'll call them slow waves. So basically, you see these waves [00:14:00] becoming larger and larger in amplitude, so basically the amplitude is up. The voltage between the zero voltage and negative or positive voltage, right? So that would be your amplitude, how big the waves are, basically, in voltage.

So we are talking about, let's say, maybe 5, 10 microvolts, a millionth of a volt during waking, all the way to 200 microvolts. So 20 times bigger than [00:14:30] you what you observe [crosstalk 00:14:31].

Daniel S.: And so, for those who didn't follow, I just want to clarify. We were talking about frequency and wavelength before, which are inversely proportional. So as the frequency gets higher, meaning more oscillations per, the wavelength gets longer. Now ... And that's kind of the x-axis. Now we're talking about amplitude, which is how high the crest of the wave is, the voltage, and these mean different things.

So we can have a delta wave, which means it's within the delta frequency, [00:15:00] at a low or a high voltage. So now help people understand if it is at a lower or a higher voltage within the same frequency range, what that means.

Giovanni S.: So we don't know exactly, right, but probably what it means, one of interpretation is that you have a lot of neurons doing the same thing. They are marching together, activated in the same time, right? So because it's basically, if you're thinking, every neuron is going to produce [00:15:30] one of these waves that is going to have the same oscillation, similar oscillations, but they are relatively small, right? Because we are talking about one single small [inaudible 00:15:39] neurons.

Now if you have a lot of neurons that are firing, that you know, we use this word when there is this discharge of electrical activity, they are firing at the same time, and this activity is coordinated, you're going to see that tall, the low, the trough of the wave and the peak of the wave, they are aligned. So they sum [00:16:00] up, right? They sum up, and they create a huge big wave.

If you have waves that are oscillating, even at the same frequency, but they are not correlated with each other, they are not synchronized, they cancel each other, right? Because maybe you can have a peak and a trough at the same time, so they cancel each other. So [crosstalk 00:16:18].

Daniel S.: So the amplitude is the sine of both many waves in the same frequency, and they are phase coherent with each other.

Giovanni S.: Yeah, they are phase coherent. They are oscillating. They are all coordinating. I use this analogy. [00:16:30] It's like an army that is marching together, at the same pace. And that is a relevant, it's a really important idea because it's relevant to what we are doing in terms of stimulating this wave, because I will explain in a moment one of our objective is increasing the amplitude of these waves, because they are associated with the benefits of sleep, basically, bigger these waves deepens your sleep.

And so one of the things that you observe, right, you were talking about cycles, [00:17:00] or there are two things. One is the oscillation of the waves themselves, and the other is how these patterns of oscillations look like during a typical night. So what you will observe is that you start to see higher and higher waves, slower and slower waves, and then this stabilizes for us a little while, and this is when you have the deepest part of sleep, that we call deep sleep, or slow wave sleep. And then all of a sudden, it's very fascinating to see when you're observing an EEG, [00:17:30] there is a very, very fast switch. It happens within seconds, almost, and the brain switch very quickly, and this will corresponds to different neurochemistry in the brain. So there are different neurotransmitters that are activated.

So it seems actually there are different regions of the brain that have a sense of time. So this time is basically about 19 minutes. So every 19 minutes, you are going to switch [00:18:00] between deep sleep to another phase of sleep, but probably everybody familiar with that, you know, this when I talk about sleep, or most people say, "Oh you're working on REM." No, I'm not working on REM. REM is what happens after slowest sleep.

So you will get to this other phase that is called REM, rapid eye movement, and it's calling this wave because when people started this phenomena, they observe that few things happen during REM. People [00:18:30] are not moving much, unless you have actually a illness where you are acting out. And so during the sleep, this phase of sleep is when you have most of your dreams, and in fact, dreams that involve you. You have some dreams during slow wave sleep. They are very different. They are not usually the typical dreams people remember, but basically you are leaving your, almost like waking life, right? You are meeting other people, [00:19:00] you are seeing things, have things happening to you.

And so during this part of sleep, you are immobile, and the main reason is because otherwise, you would act your dreams, right? And so there are actually some illnesses, where people don't have some chemicals that basically paralyze you, and actually, they punch their spouse or something, right? Because they are acting their dreams. They fall down from the bed and so on.

Daniel S.: We have seen-

Giovanni S.: So it's a syndrome, but it's [00:19:30] problematic, but usually you are immobile, and you are [crosstalk 00:19:35]-

Daniel S.: We've seen some very famous problems with this with ambien use, where people don't actually keep the sleep paralysis, so they start acting dreams out more. And there's also a phenomena of conscious sleep paralysis where people notice that they are paralyzed, where typically, in a dream, they don't usually notice, and they get scared. So there's a whole interesting-

Giovanni S.: [crosstalk 00:19:56], they see elves, and UFOs, [00:20:00] and aliens coming and abducting them, and stuff like that. So it's very fascinating, but one of the most fascinating thing from an EEG point of view is that now, all of a sudden, the electrical activity looks almost exactly what you will observe when waking.

So you start to see again very small and fast waves. In fact, in the beginning, REM was called, when it was discovered, it was called paradoxical [00:20:30] sleep. And they are EEG that look almost like if they were waking up. If you observe it more carefully, you are going to see some differences, but by eye, they look almost exactly like waking.

That kind of makes sense, right? Because your brain is doing all these activity. It doesn't have sensory inputs, but is processing all this information like if it was awake. So it kind of makes sense.

Daniel S.: Now just like in deep sleep, slow wave sleep, the primary waves are delta, and obviously, [00:21:00] there are different waves in different regions of the brain and different spindles going on, but primarily delta. And in REM, we're looking at primarily theta, right?

Giovanni S.: There is a lot of beta activity, and there is theta, but the beta, beta that is basically what people observe during waking also goes up, relatively to deep sleep, for example. So it kind of looks almost like wake EEG, with some subtle differences that people use to determine that you are in [00:21:30] REM versus waking.

And that, if you go back to what happened during deep sleep, the fact that you have these long wavelengths, basically make you unconscious, because you're not able to process the normal information that we need to process to actually be conscious. It's very interesting that, for example, lizards, when they are awake, they have slow waves. So it's possible that actually [00:22:00] lizard consciousness looks like a deep sleep. You know, like, to us, that is the most unconscious time in our life, beside being dead, or in coma. In fact, actually, coma looks very much like deep sleep or anesthesia. You have these very, very slow waves, and it seems that consciousness is associated with the high frequency waves.

And so this way, during the sleep, you are conscious, [00:22:30] and it's interesting to think about that some animals, like lizards, that go around, they respond, you know, to stimuli, but they are probably not conscious, at least, not conscious as a human being would recognize.

Daniel S.: But then when they go from ... One of the things that I understand about the reptilian system is that they go from a delta state to then high frequency spindles as soon as they move and then back to a delta state, [00:23:00] and this has something to do with being cold-blooded and needing to actually conserve energy. And so that they're hanging out in a pretty low energy state, and then they binary kick onto a high energy state, and then they drop back down, as opposed to have a higher baseline arousal. Is that a fair way to think about it?

Giovanni S.: Yeah, yeah. That is kind of what happened when they assimilated by dangerous signal or something like that. But so, and there are many other things happening [00:23:30] during sleep that I saw. For example, one of the things I noticed is that when you have this first cycle, right, that lasts 19 minutes? So you have a light sleep. Then you go to deeper sleep. So basically, there are three ... So we divide, roughly, sleep in two big parts, what we call REM and non-REM. Unfortunately, it's non-REM, almost like, okay, REM is the most important part, and non-REM is everything else, is historical, because now, nowadays, we [00:24:00] think that no REM is as important, if not more important than REM itself, but this is how we call it. And within no REM, there are three stages, right? One, two, and three, three is the deepest one, deep sleep, or slow-wave sleep.

And so usually, what happens, during the first part of the night, the slow-wave sleep, or no REM takes the majority of a cycle, and REM is relatively short. So we are talking about 19 [00:24:30] minutes, and so the majority will be more than enough will be no REM. And as the night progresses, as we come closer and closer to basically waking up after eight hour of sleep, REM would be longer. And this is why most people remember, people remember mostly dreams that happen basically just because before they woke up, unless you woke up in the middle of the night. Most of the dreams happen actually [00:25:00] at the end of the night, because this is when REM will be predominant.

Daniel S.: So just so it kind of makes sense for everyone, when we look at the different phases of sleep, the way that we actually know the phases of sleep the most clearly is by looking at people's EEG. We can also look at their eye movement, we can look at their overall body movement, we can look at breath, we can look at carbon dioxide, we can look at heart rate variability, and so when someone goes to a sleep clinic, they get hooked up to [00:25:30] the polysomnography device. It's looking at all of those things, but the real key to understand what's happening in the brain is the EEG signals.

And so if we look at most of the sleep trackers that are out there that are looking at movement, those aren't going to ... And even if they're looking at heart rate variability, then we try and look at some mathematical correlations, but we aren't actually seeing EEG. And so that's one of the really important things is our ability to track sleep right now at home is pretty limited. [00:26:00] But then each of these phases of sleep do different things, and it's amazing how much about sleep we don't know still. But we also, you know, have a growing body of understanding, and so dreaming sleep does a number of important things. There are diseases where someone has no REM sleep, and those can be fatal issues.

You know, REM disorder can be a significant issue. There's parts of memory consolidation that happen and parts [00:26:30] of psychological consolidation where information moves from the amygdala and the hippocampus to the cerebellum. But when we think of most of the regenerative processes of sleep, the physioregenerative processes, meaning when the immune system goes and cleans stuff up, when muscle tissue is repaired, when antioxidation occurs, when all the key aspects of physiologic repair and most of the memory consolidation, the learning that happened, actually moving from short to long-term [00:27:00] learning, this is happening during delta sleep, meaning more than during waking, and more than during other phases of sleep.

So really being able to understand what promotes delta sleep and being able to increase both the amount and the quality of it is one of those really foundational areas for medicine, because all of the other diseases are going to occur because of a lack of regenerative process of which delta sleep is at the core, psychological and physiologic. [00:27:30] And everybody knows what it feels like when you get really good quality sleep.

So Giovanni's work, which we're about to get into now is how do we understand delta sleep and what's happening in a way that can help us actually increase the quality of it significantly, which then can increase some very specific things that his team has looked at, like memory, but also pretty non-specifically, just a benefit of everything that's happening from sleep.

So let's get into that a little bit, and delta [00:28:00] sleep is such a valuable thing that there are lots of companies that try to put people into delta sleep, right? There's been a lot of research to drive brain waves using entrainment. So using binaural beats, or isochronic beats, or specific PEMF near the head, or strobe lights that are basically putting in a delta frequency to try to get the brain to do delta. Talk to us about ...

And I think I'd actually be surprised if many of our listeners haven't even [00:28:30] seen some delta sleep CDs out there that supposedly are entrainment devices. Talk to us about what you found about entrainment and-

Giovanni S.: So yeah, so a few things. First, I want to expand a little bit on what you were saying about the importance of slow sleep. So I fell in love with this field, because first of all, as a physicist, I love irregularities and the properties. You know, it can authorize these waves. They have a lot of interesting property. They look like avalanches, [00:29:00] for example, but it's a lot of interesting complex physics is really fascinating. But maybe we can talk about that another time if we can come another time to your podcast.

But in times of a utility of a function of slow sleep, it's almost like when I try to describe it to people, it seems almost too good to be true. But it's actually true, right? Because there are hundreds, and hundreds, and hundreds of study. Maybe people don't understand this. It's a vast field [00:29:30] of neurology and neuroscience and physiology in general.

And these are explosion of understanding of slow-wave sleep, and the [inaudible 00:29:42] sleep [inaudible 00:29:43]. So relatively new in terms of scientific discovery, but it's maybe, like, 10, 15 years that people have done dozens and dozens of studies. Just to give you a feeling, it seems that slow-wave sleep is implicated in what we call memory consolidation that I will explain [00:30:00] in a moment. But basically is the main idea is that the brain needs to select what is important to keep for long-term memory and what to throw away, and this process happens during slow-wave sleep.

So memory get ... I will describe it a little bit better, but so memory consolidation, but also some of the regenerative process that mentioned. So the body starts to heal during this time. But also, there is regulation [00:30:30] of a new system, cardiovascular regulation, hormone regulation, like, for example, there is a lot of result showing that in men, as we age, our testosterone levels go down, and they seem to be correlated to the intensity. And by the way, when I talk about intensity of slow-wave sleep, or depth of slow-wave sleep, it's basically the average amplitude of these waves. Bigger the waves, more these benefits, more of these benefits you see.

It's actually [00:31:00] quite interesting, because when people try to measure how good your slow-wave sleep is and the benefits of slow-wave sleep. All these things that are mentioned are all proportional to how big your waves are. And one of the things that we observe, for example, that is a very [inaudible 00:31:16] health, I mean, how we can improve health and our lives.

One of the things that happen with age, for example, is that these waves become smaller and smaller and smaller. Young people have huge, big, nice [00:31:30] waves.

Daniel S.: So I want everybody to kind of really note what this means here. Most of our testosterone production is occurring during slow wave sleep. Most of our human growth hormone release and spikes are occurring during slow-wave sleep. Most of our muscle tissue regeneration, organ tissue regeneration is happening. Also, killing the old senescent cells, the old cells that start throwing error codes that are associated with aging, the process called autophagy, much of that happens [00:32:00] during slow-wave sleep.

Cleaving the old synapses, which allows new learning and plasticity happens during slow-wave sleep. And so now, as people age, and many of us are aware that older people need less sleep. Well, it's not that they need less sleep. It's that they are sleeping less, and they're aging. And children are profoundly regenerative and growing, and are sleeping more.

And the amplitude of delta is a [00:32:30] huge part of that. And amplitude specifically, not just the total amounts of sleep, but the intensity, the sleep quality of the deepest part of sleep is a huge part of it, and so of course, there's something with aging that's making people sleep less. But then the sleep itself is causally increasing those things, so there's some feedback mechanism. But if we could increase the quality of delta sleep, the amplitude by itself, all of the things associated with regeneration and anti-aging would increase. So that's kind of a big deal [00:33:00] across the board.

Giovanni S.: And there is some research. In fact, it's probably actually one of the main function of slow-wave sleep, reduction to get rid of toxins. So there is a build-up of a lot of toxins in the brain, right? Like is a byproduct of the fact that we have metabolism. My cells have to process energy to function, and there are waste products. And these waste products, until recently, [00:33:30] people didn't even understand how the brain could get rid of these, because there is not the typical [inaudible 00:33:36] ...

Daniel S.: Lymphatics.

Giovanni S.: Yeah, almost all the other organs have. So they discovered there are channels that the brain can use to get rid of these toxins, but again, this process mostly happen during slow-wave sleep. And so there is a nice TED Talk that talks about exactly this, that is actually probably [00:34:00] one of the main function of sleep to get rid of toxin. And there is a series of studies that came out recently, one from Berkeley, from actually somebody that graduated from our group who is a postdoc at Berkeley, and they did this very nice research where they show that there is almost, like, a vicious circle, so one of these feedback loops between [00:34:30] accumulation of toxins that is deteriorating the brain, the brain circuits, the brain networks. That deterioration produces less slow waves. Less slow waves get less rid of toxins but actually create even more deterioration of the brain.

And so the slow waves, lack of slow waves, is a mediating factor in producing even more deterioration. So people that have problems in getting rid of these toxins [00:35:00] usually develop diseases like dementia, Alzheimer, and so on.

So one of the possible applications in enhancing slow-wave sleep will be to get rid of these toxins in a more efficient way, and so maybe less aging in the brain, and actually, I don't say curing, because it will be amazing [inaudible 00:35:22], but at least are helping ameliorate conditions like Alzheimer's, for example.

Daniel S.: So that vicious cycle is basically called [00:35:30] aging, right? And for those who haven't already inferred this, one of Giovanni's great passions and interests is the topic of radical life extension and anti-aging, and it doesn't surprise us that he ended up focusing on increasing the quality of delta sleep, because it's kind of at the bottom of this stack of the things that would affect this, because if you think about it, you're like, "All right, we're trying to affect longevity. Do we try and elongate the telomeres? Do we [00:36:00] try and deal with oxidative damage? Do we try and deal with brain toxicity? Do we try and help get rid of the old cells that throw bad signal, increase autophagy and apoptosis? Do we try and create new tissue synthesis? Or can we do all those things?" It just happens to be that the body does all those things during delta sleep.

And so if you can increase the quality of delta sleep, then you're basically just increasing physiologic regeneration comprehensively, which means decreasing aging and probably [00:36:30] all cause mortality.

Giovanni S.: Correct, so and again, I know this seems too good to be true, but actually, it turns out to be true, because there is a lot, a lot, of research supporting this topic. So it's very fascinating. So I want ... and this kind of almost leads me to the next topic I saw.

There are many claims on the internet saying, "Oh, delta sleep, right, will help you do this and help you do that." And then you can do this [00:37:00] very simple thing that is listening to some cities that will help you with your delta sleep. So my conclusion about that is that a lot of these claims are not why the science behind slow wave sleep and importance of slow-wave sleep is very developed, and there are a lot of study proving these are fundamental of slow-wave sleep. These are simple solution of listening some background [00:37:30] music that has a lot of oscillations, hold your oscillations in the range of delta frequency using binaural beats or isochrones is actually not true.

So we tested, and we did a lot of testing. We actually bought some of these CDs, and we played them, and remember, the gold standard to see if something really happens is actually looking at the EEG, [00:38:00] because if I play a CD and I see a change in the brain activity, but if I [inaudible 00:38:06] now I see that maybe bigger waves, then that could be scientific evidence that these approaches work. If I don't see anything between not playing the music and playing the music, then probably [crosstalk 00:38:22].

Daniel S.: So you have someone hooked up to an EEG, you play the delta binaural beats or the delta isochronic beats, and you did not see increase in total [00:38:30] amount of time in delta or amplitude of delta.

Giovanni S.: 99 of the products that are there don't work, and exactly. Exactly because of this, we don't see changes.

Daniel S.: Now you have a hypothesis as to why driving brain waves, not just delta, but any brain waves, is not a really easy thing to do, why the brain resists it, and why there's a better approach.

Giovanni S.: Yes, so-

Daniel S.: I think this is fascinating.

Giovanni S.: So if you back to these oscillation [00:39:00] that I described before, right? So even if we are really in a range of frequencies, it's not really what we usually think. Probably even the name wave is a misnomer, because what you are going to see usually is like a change in voltage, right, that is happening in a more or less rhythmic way. But this oscillation, each single oscillation is different. So you will have one that [00:39:30] takes maybe two second. Let's say that you're in delta wave, one that takes two second, the next one will take maybe half a second, and the next one, it's one third of a second. So if you are thinking about a normal wave oscillation, they are almost all, all these oscillation, they are all at the same rhythm, right? They [inaudible 00:39:49] maybe if you are talking about the sine wave, they will always have one second oscillation if this is one hertz wave. It doesn't happen like that with [00:40:00] the brain.

And so probably what is happening with populations of neurons, they are activated and deactivated, activated, deactivated, but it's a very complex network kind of behavior, and in fact, if you study the physics of it, right? If you are trying to understand the distributions of these frequencies, when they happen, how they happen, how they are related to each other, it looks almost like very complex system, like maybe [00:40:30] avalanches, like or earthquakes, right? Earthquakes are very similar for example, in terms of when to expect the next big earthquake. They are very complex, this entire branch of physics is called complex systems. It's a very, very ... They are very interesting tools that you can use.

But the idea that you are talking about, very regular oscillation, is not true. And so if you are trying to apply a regular oscillation, that [00:41:00] is basically what most of these CDs do, that is not related to what the brain is doing at a particular time, even if it is in the same range that you are trying to activate, let's say you are playing tones that are happening once every second. So you are in that frequency range that you are trying to increase is not going to ... The brain is not going to respond to that. Yes, maybe it's going to hear that tones, and so if you look at the spectrum, you will see maybe a spike at that particular frequency, but [00:41:30] it's not doing anything in terms of driving the brain.

It's not doing anything in time to push into the brain in a certain direction, mostly because the brain, remember, we talk about these rhythms as almost a language for the brain. It's what the brain uses to communicate with each other, so it doesn't really ... And one of the most important ... You know that very well, because I've heard you mention it so many times in other talks that you gave. It's a fundamental principle of physiology that the organism tries [00:42:00] to stay in the same state, right? We talk about homeostasis. The brain, the body tries, the physiological systems try to stay in a state of equilibrium, and if you are pushing it too much away from this state of equilibrium, it wants to come back, and it is resisting these changes, right? Whatever the changes in temperature, the changes in chemistry, or whatever.

So if you're trying to push your brain in a very forced way, right? In physics, [00:42:30] you can drive a system. Like, you can try to make oscillate a swing, for example, right? You have a swing you are trying to make it go back and forth [inaudible 00:42:39], you're going to push it, right? You're giving a push to the swing, and the swing would start to oscillate. But you can drive it at the particular frequency, and it's a mechanical system, and the system will respond, but the physiological system, if you're trying to do the same thing, where you're applying a very regular push, is not going to respond very well.

And so that [00:43:00] directly is a ... You know, in neuroscience, a lot of things are so complicated that we can just use explanation of this kind, that I think are general, a bit ... They are not going ... There is not an equation that I can write down and say, "Hey, this is how the brain responds." People write complex mathematical models with thousands or hundreds of thousands neurons and do simulations. That is the closest that we can come to an explanation of what [00:43:30] is going on.

But from a quantitative point of view, you understand, right? That this is how the brain will respond. It's not a swing, a simple pendulum, where you can push it and make a swing at a particular frequency. It's something much more complex. So you have to do something more sophisticated.

Daniel S.: So I'm going to just restate this in a way that hopefully is very clear for people. So when we see that specific brain wave patterns mediate specific kinds of processes, and that the delta brain waves that mediate [00:44:00] the slow wave sleep mediate so much physiologic repair and regeneration, we could easily see why we would want to try and push somebody into delta, right? Push them from some lighter sleep into delta.

But that's not the only type of brain waves that people try and drive. There are meditative states that we've found by looking at people's qEEG patterns while meditating, and then maybe try to drive those states.

So there are a bunch of technologies that either use strobe lights in the eyes or that use [00:44:30] sounds in the ears and different kinds of sounds, the binaural beats play different sounds in each ear, hoping that the difference between the two sounds is will induce a frequency in the brain, and then you have ones that will use both, light and sound devices.

And I'm not going to say that there is nothing good that can come from that whole field, but it does make sense here to say the brain is regulating itself in this profoundly intricate complex way factoring that we understand only little [00:45:00] bits of, factoring a tremendous amount of data that we don't have.

So when we say that someone's in delta sleep, like Giovanni was saying, that doesn't mean that they have a perfect two hertz sine wave. It means that it's going from half a hertz, to four hertz, to 2.1, to 2.2. It's moving around with a lot of coherence based on a lot of internal feedback, and it knows what it's doing a lot better than we would know kind of how to drive it.

And so we kind of need to do something else where we pay [00:45:30] attention to what it's doing and help it do it better, which is the insight that Giovanni's team took, which was rather than try to drive brain waves, let's see if we can follow them and help them, and this is where amplitude kicks in. And this is where I think this is really a breakthrough field of research.

So if you would, talk about what following the brain and helping it, and the phase lock process is all about.

Giovanni S.: So the idea here is training very well, right? So basically [00:46:00] the underlying concept will be, okay, probably the brain knows what it's doing. So maybe even the fact that what you just described, like, we have a four hertz wave that is followed by 2.1 that is followed by a 3.1, maybe that is information itself. Maybe it's actually a way of encoding information that is happening in the brain, because we didn't go too much in depth in that, but one of the things that we very interested is this process of memory consolidation, [00:46:30] right? Where [inaudible 00:46:31] basically information that has just been acquired by the brain that is stored in the hippocampus. It's a region that is associated with memory. So the brain restores temporary memory in the hippocampus when ... It's a very complicated process, but I'm going to simplify. Basically, it's some kind of transfer of information from the hippocampus to the cortex, and actually integration of new information and old information.

So if you learn [00:47:00] ... So today people learn about my name, Giovanni. At night, they are going to think about that, talk, and the brain is processing this information, and there is a region of the brain that is all the Italian people that I ever met in my life, right? So this new Italian guy will be integrated with that information that has to do with Italian people, or being Italian, or having an accent. And so new information and old information gets integrated during this process that is also, [00:47:30] basically, it's the basis of creativity.

You know, so when you make new association when you are thinking about new ideas. This is why people sometime come up with new ideas once you go to sleep, right? You wake up, and you're refreshed, and you're thinking about a new solution to a problems that you've thought for a long time.

So it's not just about remembering better and for longer time, [00:48:00] this process of consolidation of memory, also it's a creative process of associating holding new information. But so this process is happening with these rhythms, these very specific rhythms, and we don't understand them. We just know that they are there, and they have certain properties.

So the last thing that you want to do probably is to interfere too much. So if you're imposing a rhythm that you think is okay, like, why one hertz? Well, because it's in the center [00:48:30] between 0.5 to four hertz, which is the delta band. So most of these CDs will play a very specific frequency, or maybe they will change slowly the frequency, but this, a human being deciding, "This is what the brain needs to do." Right?

So our idea was, "Why don't we don't have the brain tell us what is the right frequency to stimulate the brain itself?" So we basically, we call it close-loop stimulation. We follow the EEG, we track the EEG in real time, [00:49:00] and then we use the brain rhythms during deep sleep to stimulate the brain itself. It's almost like if I'm playing back your own brain rhythms. And what that does, it's enforcing these rhythms and make them more regular, and it's almost like if you had an army, like my analogy before, and now everybody's marching, but you have a drummer, right, that is giving [00:49:30] a certain rhythm, and everybody's following that, but the drummer is also looking at everybody marching, right?

And so there is a back and forth transfer of information, right? So if everybody starts to a little bit faster, the drummer is actually following that march of a army, and you go back and forth in this way. So it's a closed-loop stimulation, because you follow what the brain does, we play back these rhythms to the brain. That [00:50:00] seems to make the brain even more regular and amplifies the wave, and then it somehow slightly changes the rhythm to actually slower frequency without actually the most beneficial, and now our playing back of these sounds ...

So basically, you can do [inaudible 00:50:23] using many paradigm. You can use electrical impulses. You could use maybe other [00:50:30] type of information, like flashes of light, or whatever. But what we have used with a very high success, it's sound.

So the idea of using sound during sleep to enhance brain rhythms, it's actually true, but you have to do it in a clever way. You cannot just do it by playing in the background without considering what the brain does. So that will be a ... If you want to call [00:51:00] it an open-loop stimulation, right?

Daniel S.: So just-

Giovanni S.: [crosstalk 00:51:03] close the loop, you do it independently of the brain, of what the brain does moment by moment. That type of stimulation doesn't work. [crosstalk 00:51:11]-

Daniel S.: So just say briefly why, from an evolutionary perspective, sound is a meaningful way of stimulating the brain during sleep.

Giovanni S.: Yeah, so first of all, it seems that there is a pathway from the auditory brain, right, there is a part of a [00:51:30] brain that is processing auditory information. It goes to this region of the brain that is called the thalamus, that is almost like a relay system for sensory information. Everything goes, that comes from the senses, goes through the thalamus, and then from the thalamus goes everywhere else in the cortex in the brain.

So there is a pathway that goes from the thalamus that is coming from the auditory system that goes all the way directly to [00:52:00] the cortex and is independent from the normal pathway that processes sounds. And as one main function, that is actually very similar to other interesting pathways that people discovered. One relevant one is, for example, is a pathway that goes from the eyes to a part of the brain that regulates rhythms, circadian rhythms, or physiological rhythms, and that pathway does one, only one thing, that is resetting this physiological [00:52:30] rhythm. And something like that has been discovered recently.

So we know of a similar pathway that does only one function, and this function is to alert the brain of a danger when you're sleeping. So you're thinking about, right, so it seems that sleep has all these important physiological functions, and so it's very fundamental for the organism, for an animal, to sleep, right? But it's also very vulnerable time.

So if we're thinking [00:53:00] from evolutionary point of view, you had in a full rest, you're taking time off, you need to regenerate, you need to do all these consolidation processes in your brain, but you're exposing yourself as an animal to predators, because you're immobile, you're not sensing the environment very well. So it's a trade-off, right? There is a trade-off there between all the benefits of sleep and exposing yourself to predators [00:53:30] and kill you.

At the same time, the brain develop a system that can monitor the environment. So even if you're not monitoring the environment like if you were awake, or with your eyes, and all your senses, at least one sense is still devoted to monitor the environment. That is basically the auditory system.

So you're still hearing around you, particularly for humans, right? We don't have a very good sense of smell. We cannot touch things around while you are sleeping. [00:54:00] So we are closing your eyes of a [inaudible 00:54:03] that is still working, and probably there is a reason why we cannot, unless you have earplugs, you can stop, right? I can close my eyes, but I cannot stop hearing stuff.

And so when I'm sleeping, I'm listening to the environment. So people discover, again, by just having EEG ... So in particular, with, you know, they have some people that need to be followed [00:54:30] all day long during the night and during the day. These are epileptic people with epileptic. So they put electrodes inside of the brain, and they follow you for days and days to look for the source of an epileptic attack. There particular region where an epileptic attack happens.

So we have days and days worth of EEG data for these subjects, and one of the things that was discovered when they were sleeping and there was [00:55:00] a nurse knocking on the door, you saw all of a sudden a negative drop, a drop, negative drop of the voltage of EEG. And remember what I said before, right? That is the resting state of the neurons. So it seems when you hear a sound, a loud sound, sudden sound during sleep, all of a sudden, all the neurons go down. They go in this resting state [00:55:30] in a very coordinated fashion.

So it's this auditory pathway that sends this message and tells to the brain, "I just heard the sound." Compared to sleep, but I'm looking at ... I'm monitoring this. I'm-

Daniel S.: So there's this evolutionary reason why the brain is still processing information from the ears at night compared to, differentially, compared to the other senses. And so [00:56:00] we're able to use this as a way of putting input in, but it has to be the right input, which we'll get into a little bit more in a minute.

But there is actually a piece of applied value here that I'll make sure everybody catches, which is this is why sleeping in a quiet environment and or having a white noise generator is so important to sleep quality, is if you're in an environment where the dog barks, where your partner is snoring, where loud noises start [00:56:30] to happen, every time that occurs, you will drop from a deeper sleep to less deep quality sleep to see, "Is this something that I am actually going to have to have a survival response to?"

And so just one very simple thing, since Giovanni's device is not available for purchase yet, that you can do to make sure that your sleep is not being disturbed without you even knowing it is make sure that you control the sound in your sleeping environment.

Giovanni S.: Right, [00:57:00] and so I thought the sound that we describe has to have certain characteristic to wake you up, like, for example, if you have a sequence of sounds that are going to be louder and louder, it probably is a predator that is coming closer and closer, so wake up, right? So the brain listen to these sounds, can process information, like, for example, an increase in loudness, and then that would be a signal that you need to wake up, to pay attention to that sound.

If there is a sound that is [00:57:30] repetitive and is in the background, then that cricket noise for example, right? That you hear it, the brain is aware of that sound, but it discards that sound as dangerous, because it's probably a background noise.

And so basically, this is what we are hacking. It's an hacking of these very precise pathways that goes directly to the cortex, where actually, the slow waves are generated, but the [00:58:00] secret, the secret sauce that we have is the timing. So you have to deliver these pulses of sound, and sound is actually given ... There is this pathway, given that the brain responds so strongly during sleep to sounds, it's actually the best way to stimulate the brain.

So people have tried electrical stimulation. They've tried ... Some of these things work. There is a beautiful paper, Nature, that is one of the most ... You know, the most important [00:58:30] science journal there, and they most said that you can use electrical stimulation to actually announce these slow waves.

But it's very invasive, the slow waves that are generated by electrical stimulation that look exactly like the endogenous and natural slow waves. When you do it with sound, and in particular, if you do it correctly, and correctly means, as I say before, you have to follow the rhythms of the brain. So it turns out, by just experimentation, right, many different things, [00:59:00] that you have to deliver the sound at the particular part of these oscillations.

So let me explain that in more detail, because it's kind of crucial. So I [inaudible 00:59:10], when you see the negative phase of a EEG, this is when the neurons, most of the neurons, collectively, you know, we're talking about when you have an electrodes, you are measuring the electrical activity of millions and millions of neurons, just below the electrode.

And so you see this negative voltage. It's probably the reason behind [00:59:30] it is that many of the neurons are in their resting state when they are negative voltage. In a sense, the neurons are sleeping during that time.

So it's very interesting, right? They are sleeping, so if you are thinking about this oscillation as roughly once a second, right? Even if you are not precise [inaudible 00:59:49], just for simplicity, we can say half a second. So for half a second, they are sleeping, and they are sleeping all together, and then, for the other half [01:00:00] a second, they are firing. They are communicating with each other. They are creating these electrical spikes of activity, and there is information that is moving from one part of the brain to the other, and this happening the other half of this oscillation.

So we call the downstate when it's negative and the upstate when it's positive. This is when the information transfer happens. The negatives part is when the neurons are taking a break. [01:00:30] So they are resting. They are doing all the different things that they need to do when they are resting. Then they are not taking off all the time. They are saying, "Okay, half of the time, we are resting. Half of the time we are going to do something useful. Let's do this activity."

And they are talking together, they are communicating with each other, and this happens during the positive phase of the oscillation, the upstate. And it turns out if you deliver [01:01:00] the pulse just before the peak of a positive wave, alpha wave, this is when, actually, you see an enhancement. So if you observe an enhancement of the amplitude, and with that enhancement, we see a lot of the physiological benefits of sleep.

So in particular, we wanted to see if ... So we were able to [inaudible 01:01:26] state with this particular type of stimulation. So you have to have [01:01:30] a way of tracking brain activity. So we use an electrode here. We tried to minimize the number of electrodes, so if you see some pictures of this neuroscience experiment where people EEG, you see a lot of electrodes all over the plain, but that is mostly to see what the brain does in different brain regions.

But we try to focus in our experimentation in our research to use just one single electrode, because we have always in mind to create some kind of device that people could use [01:02:00] at home, so less electrodes you have, better it is. So we all what we need is just one single electrode here on the forehead, where most of the slow waves are produced.

So we track in real time the behavioral thought of these waves, and we observe, we'll actually even predict where the peak is going to be, with the lever on a pulse of sound, and that pulse of sound is very small. It's about 50 milliseconds, so it's a very short, fractional [01:02:30] sound. It sounds like [inaudible 01:02:32], like this, and it's a pink noise. The fact that this pink noise is not fundamental, it's a pleasant sound, but probably so short that the brain doesn't really distinguish if this is a pink or white or Beethoven music. It's so short, right? But it produce an electrical response, because basically, they, when it arrives [inaudible 01:02:56] here is the signal starts forming an electrical signal. It goes through these [01:03:00] specific pathways, and it's exciting the neurons.

So imagine you have this electrical activity already going on. You are adding a little bit of energy on top of it, and that makes this firing of neurons even faster and more coordinated. It's almost like, you remember he made this analogy with the avalanche. It's almost like you're going on a hill where there is a lot of snow that is ready to fall down in an avalanche, and you go [01:03:30] there and you scream, right? You say, "Ah!" Like or something like that, and that sound, that little sound pushes a little bit of snow, and that little bit of snow, even microscopic amount, right? Creates ... Pushes other snow, and you create an avalanche.

So you're just adding a little bit of energy to push the system in a very gentle way, in a very noninvasive wave, and that does an enormous effect, because you see increased increments of these waves, [inaudible 01:03:59] and [01:04:00] enhancement of these waves that sometimes, for some subjects, is two times. You see two times bigger waves.

And the idea is that, in the past, when people were looking for ... So it was being demonstrated before, right? So there was a sequence of papers and studies that came out. So first people noticed that you remember better after a night of sleep. So you're ... If I give you a memory test and you take [01:04:30] it early in the morning, then a test eight hours later during the day, and then I compare your performance with the same type of test if I give it to you in the evening and then I test you in the morning after eight hours, you do much better in this second case, where I give you the test and then you ready for same amount of hours pass by, you know, eight hours, if I test you in the evening, and then I test you again in the morning, your performance will be better in the morning, [01:05:00] relative to people that took the same test during the day.

So we went some demonstrations through experiments like these that sleep has a benefit to memory. Your scores will be higher in the morning than in the evening, and when people try to understand what physiological ... If it was any physiological evidence or any physiological parameter that they could measure that related that to this improvement in memory, [01:05:30] they found out again by trying many different things that the average amplitude of these waves during slow-wave sleep correlated with the performance in this memory test.

So this is by not doing stimulation, right? Sleep alone. Sleep alone shows that there is a correlation between the average amplitude of a person that sleeps and how they perform in this memory test.

Now the idea is what happens if [01:06:00] we increase the amplitude. Do we see an improvement in memory? Yes, you do. And so this is one of the first things that we tested once we were able to show that actually the stimulation improve, increases the amplitude of these waves. We wanted to see if that increase in amplitude corresponded to an improvement in memory.

And yes, we had a very nice where, in particular, with older people, remember I told you that older people have very, [01:06:30] very small waves, so it's a very well known thing, right? That there is a quantity decline due to aging, and a lot of the cognitive decline can be associated, it can be correlated, it can be statistically, you can show that has to do with this decrease in slow-wave sleep. If you take two older people with similar ages, and you compare their slow-wave sleep, the person that has poorer slow-wave sleep [01:07:00] has measure with the amplitude, like, with a [inaudible 01:07:03].

It's not even how much time you're spending in slow-wave sleep. It's the amplitude of these waves. The person with smaller waves will have less ... You know, they will perform worse in this memory test.

Daniel S.: Okay, so before you go to the next [inaudible 01:07:21], I just want to recap the key points here, make sure that they're clear for everybody, and then we'll actually share what the ... Have you share what the results were on [01:07:30] memory.

So a few really key things here. The idea is that we're not just interested in how long someone is in delta sleep, right? The frequency, but we're interested in the amplitude of that frequency. And if you just kind of roughly think of it as that the amplitude corresponds to how many neurons are firing in coherence with each other, it kind of represents the total efficiency of what's happening, the effectiveness of what's happening.

So 30 minutes of really poor quality delta [01:08:00] versus 30 minutes of very high quality delta are very, very different, right? And so that's one kind of key insight that's different in the way most people generally think about it is just the amount of time in a specific phase. Here, we're looking at the actual quality of that phase. That's one thing.

The next thing is that there's a philosophically really kind of beautiful approach that says, "Hey, the brain is actually pretty smart. It knows what it's doing really well, and rather than just try to push it to do what we think it should do, [01:08:30] let's follow what it's doing and just give it support." And it is a much more go with the body and support it rather than trying to override it, which is, I mean it's core to the Neurohacker philosophy everywhere. How do we upregulate the regulatory capacity rather than override?

And so rather than say, "Here's a frequency that the brain isn't doing, and we're going to try to make it do it," it's saying, "Let's measure what the brain is doing and give it exactly what it's doing in feedback," right? Just feedback to it what it's doing so it [01:09:00] can do what it's already doing better.

And there's two real key concepts there. One is that the brain is not susceptible to really take information throughout the entire cycle. Only at the crest of the wave when the gates are open is it susceptible for input, so we're not playing the input all the time. We're playing the input when it's open to input, and then we're actually reading the brainwave patterns and giving an input that is exactly what's going [01:09:30] on in the brain at that moment. So we're feeding back to it a frequency that is proportional to the frequency that it's in.

So if someone is in delta, delta still isn't one thing. It's this variable thing, and so we're giving mirrored feedback, and that's why it's called closed-loop or phase-locked induction. We're putting back in a frequency that is the same frequency the brain is in in a phase-locked coherence with the brain, which drives the amplitude. And driving the amplitude drives the efficiency of that phase [01:10:00] of sleep.

Now we've already said that pretty much all kinds of interesting things are associated with delta sleep, so we ... Giovanni could have probably done a study that showed when doing this, human growth hormone went up. Hasn't happened yet. Probably could have shown one on testosterone. Probably could have shown one that showed that beta-amyloid goes down or that inflammatory markers go down. But the first study was on memory.

And I really do think it's fair to say if we're not focused [01:10:30] on memory specifically, we're focused on sleep and increasing the quality of sleep. Memory is one of the indicators, that all the other indicators associated with sleep, very high probability that when we test those, we'll see them show up positively.

But now, please tell us what you found when you did the sleep in younger and older populations.

Giovanni S.: Yeah, so the first thing I want you to elaborate a little bit on is phase lock loop, exactly. So in fact, to do this type of feedback, [01:11:00] you have to be clever. You have to use an algorithm, right? Because you want to be a little bit predictive. So that is one of the things that it's key to our approach. In fact, we have a patent. We have a IP associated with applying ... We didn't invent these specific algorithms called a phase lock loop. It's used in electronics everywhere to synchronize basically two clocks, like, in your computer, in many devices, there is this algorithm [01:11:30] that is called a phase lock loop. We adapted the phase lock loop to this particular simulation. We had to change it a lot, and understanding how the brain works, make it work for this specific application.

But that is what we are doing. We are using this clever algorithm that follows the rhythms and then knows, and in fact, can almost predict, basically, where to deliver the next pulse, because you want to do this in realtime, and there would be some delays, et cetera, so you need to opt [01:12:00] to be a little bit predictive of understanding what the brain will do next and deliver the pulse at the right time.

And the focus on memory was exactly as you explain it. Because there are so many benefits due to slow-wave sleep, we could have done many different experiments showing that this happens when you stimulate the slow waves, that you see an increase in these beneficial hormones. You see a decrease in this [01:12:30] negative biomarkers and so on.

And in fact, we want to do all that. Eventually, we want to show that, yes, here, we have a clinical study showing that testosterone studies increase when we do the stimulation. It's just that you could imagine these experiments are pretty complicated, and it takes time.

Memory is kind of a low hanging fruit. It's one of the most known, at least in the field, not in the general application, even if I know it is more and more media coverage [01:13:00] on this link between memory and slow-wave sleep, that there are a lot of articles coming out recently on this topic. But it's one of the best known effects of slow-wave sleep that it improves memory.

So we wanted to show that now because it could have been, right, like, always in sine, you see a correlation, right? When you do these studies when you see an improvement in memory, and then they strongly correlate with the amplitude [01:13:30] of the waves. Correlation doesn't mean that there is causation, right? That actually the waves themselves, they produce better memory.

Now there are still probably just a sine, like you say, of how effective this process of memory consolidation is. But we wanted to see if by increasing these waves, there was actually an improvement in memory. It didn't have to happen, right? It could [01:14:00] be simply a correlation, and indeed, that is exactly what happens, so when we improve these waves, we gave a memory test, right? So basically if you want to ... A little bit of the details, we give a battery of tests, but one of the most classical tests is basically word pairs. We give you two words which are associated with each other. You know, they come up on the screen very quickly, every four seconds. You have to pay attention, and you see hundreds of these word pairs. [01:14:30] Then in the morning, randomly, we show the first word, and you have to tell us the second word.

And then we measure your score. And so our usual protocol is people come to the lab. It's just two nights. One night, they are stimulated. We randomize which night is first, because it could be an effect of when they actually had the stimulation, so we randomize that. So one night, they get the stimulation, another [01:15:00] night, they don't get the stimulation. And we usually see, like I said before, an improvement due to sleep alone.

So let's say, for example, in the evening, I show you 120 of these word pair, like grill steak, right? And then in the morning, I show you the word grill, you have to say steak, and that will mean that you remember this pair.

So I'll say that in the evening, I give you this test. I show you these 120 pairs, [01:15:30] and then I test you, and maybe you remember 60 words. Now we did this experiment with young people, we did it with older people. Older people tend to remember less words. So maybe a typical older person, and with older mean 65 and older.

So a old person comes to the lab, and maybe they will remember 60 words after the test. Now in the morning, we test them again. We [01:16:00] randomize the order of these words. Again, we count how many of these words they remember, so maybe a older person goes from 60 pairs in the evening to 65 in the morning. So they remember five words, five word pairs more. And that by, by sleep alone, without any stimulation.

Now when we stimulate, in the evening, they will remember, of course, the same number, because it's kind of, in average, [inaudible 01:16:31] [01:16:30] perform more or less the same. In the morning, they go from, like I say before, 60 to 65. Now they will go from 60 to 75.

So that five words improvement, now it's three times, and sometime even four times, like 20. So they go from 60 to 80. So typically, in average, we get an improvement of three and a half, four time what ... So it's increasing four times [01:17:00] of improvement due to sleep alone.

So in a sense, you can say that the efficiency of this process went up by a factor of four.

Daniel S.: So there's different ways that we could look at the statistics of this, but to say that we're increasing the efficiency of sleep on memory consolidation by 400% is not an unreasonable way to talk about [01:17:30] it, and to just have a sense of what that means, like, 400% more effective sleep, from the point of view of this particular aspect of memory, and then we can say it might be less than that, it might be more than that for many of these physiologic dynamics that we're looking at. To me, this is just so profound, right? Like, not just decreasing the likelihood for [01:18:00] dementia and Alzheimer's, but also neurodegeneration, also psychiatric health and wellbeing, which is so deeply correlated to the quality of someone's sleep, and so many things, for longevity and disease states. Somebody gets poor quality sleep is associated with increased risk of cancer, autoimmune, neuro degen, psychiatric disease, all forms of complex disease, and all cause mortality.

So yeah, just I [01:18:30] want to kind of share with the listeners here. Some of you are listening to this just because the science is interesting, and some of you are listening because it is cool to know what is up and coming with the tech. So DeepWave is working on getting this tech actually ready for consumer application soon, and this will look like, you know, a small little EEG monitor on the head and some inputs that go into the ears. Industrial design might look different, might be integrated into a sleep mask or a headband.

[01:19:00] But imagine if we're actually talking about something, like a 400% improvement in sleep quality, memory associated with sleep quality and other things like that, and again, this is even early in the research. So as soon as we met them, the Neurohacker team was really impressed with this DeepWave research, and we've been exploring how we can help and partner with it and advance it.

I'm [01:19:30] going to ask you, Giovanni, in a minute, to talk about the associated tech, because I know that the first part of the tech is this phase-locked induction. And even though it's been focused on delta sleep because, right, that's so regenerative to everything else, you could use that for any kind of brainstem. You could use it for reinforcing performance during high performance states, right?

So the same capacity that allows us to increase the amplitude [01:20:00] of delta could allow us to increase the amplitude of any brain wave state, which is just, like, it's basically an entire category of technology that is working with the brain and the topic of brain waves differently, that is really working with understanding what the brain's doing and mirroring it, following it, supporting amplitude.

I'll just kind of state that we have a pretty awesome network of people that our friends I'm associated with, the Collective in podcasts, so I'll just [01:20:30] kind of put it out there to you, I think that sleep tech done well is, from a economic point of view, a trillion dollar field. It has applications to every disease state and every wellness state that exists, so it's kind of a big deal, and we're actually working on a number of different types of technology at Neurohacker for sleep right now, but there's ... I don't think there's any of them that I'm more excited about the total potential of [01:21:00] than this, because this hasn't ... All the side effects are positive, right? Because you're not trying to drive a specific chemical.

You're actually helping the brain just do what it does, which will create lots of chemicals, and we don't understand exactly how adenosine and orexin and long-term potentiation and the cholinergic processes and all those things work well enough, the melanocyte pathways, so we can work with the chemistry of the brain, but if you actually just get the electrophysiology of the brain down, and all of the chemistry [01:21:30] is getting dialed in, it's just such a profound thing. So any investors and scientists that want to play, I would highly encourage you to check out what DeepWave is doing. I think it has tremendous potential if it can take what it's done in the lab and bring it to consumer applications.

Giovanni S.: And these technologies are not one against the other, actually, they can work together like if you have a supplement that can help sleep, right? That is [inaudible 01:21:59] and supporting [01:22:00] the neurochemistry, when use our device, could make it even more efficient, and it can be, instead of being a vicious circle, can be a virtuous circle, right?

Daniel S.: This is a study I plan on us doing together soon. When our sleep product comes out and your tech is ready.

Giovanni S.: Yes. So yeah, it's basically the same philosophy. You're helping and supporting what is already pretty much optimized, right? You can enunciate, [01:22:30] you can make it better. In particular, you can, let's say, in particular, with the idea of aging, right, where unfortunately, there is a decay of processes that are not there maybe optimized, but when you are young, right? And when you are older because of, maybe it's programmed, maybe aging is programmed to kill us. Maybe it's just simply decay.

But there are a lot of negative side effects, and you want to help with that, right? But you want [01:23:00] to do it in a noninvasive way. You want to do it in a gentle way, right? If you want to kind of respect the intelligence of a system that is already there, and this is what we do. We work-

Daniel S.: Just to kind of have a sense from life extension point of view, programmed cell death is probably ... I mean, not programmed cell death, programmed death is an unknown topic. It's probably the case, it's probably tricky. Maybe we can deal with it just with molecular mechanisms, but making it past 120 is [01:23:30] a whole different thing than making it to 120 well. Making it to 120 well seems near term realizable. There's a gazillion things that can be done. You've got [Rad 01:23:39], and SENS, and the Methuselah Foundation, and Calico, and lots of groups working on it. There's a lot of research that's already good. I take the right kind of neuro anti-inflammatories and neuro detox support, and I take Depranil, and Epitalon, and TA-65, and so many of the things associated, I would take improving the quality [01:24:00] of delta sleep over all of those combined if I could, because it is just deeper in the stack to how all of those things are endogenously regulated.

Giovanni S.: And by the way, we are doing some studies where we are looking at a lot of the neurotransmitters and hormone stuff. We are looking at brain generative factors. You know, we are looking at [01:24:30] BDNF, for example. We are looking at cholesterol. We are looking at many different effects. So we are looking at these markers, biomarkers, of inflammation, or generative ability of the brain to create new neurons. We're looking at all these, neurochemistry, that maybe is enhanced by our stimulation. So [01:25:00] we are doing this stuff, and so we want to do more of this stuff.

So yeah, I mean, it's really interesting, because it's one of the less invasive thing that you could use that is sound. It's natural, we are doing it in a very noninvasive way, and we are getting this amazing physiological result. We are not talking about small improvement in performance. We are talking about huge big effects.

I got some criticism. So [01:25:30] for example, when we did ... We got a lot of press coverage. We were everywhere. Actually, if you go to our website, it's deepwave.tech. We have some of the press coverage about the studies that are behind the science of DeepWave, and we were featured on Times magazine, on the Smithsonian, on ABC. We had a lot of nice coverage, but yeah, because there is a lot of interest in this topic.

[01:26:00] But the idea is that we're getting these big huge results with a very, very noninvasive approach, so it's, in terms of, for example, it's much better than a drug. It's much similar to a supplement, right? But a supplement that is extremely efficacious, like Qualia. So we have the Qualia of sleep, but without using chemistry, [01:26:30] right? Well, at least, not directly.

So it's very active are these results, and how the science is going. It's exciting.

Daniel S.: Well, I'm excited to update the Neurohacker listeners as the results come along, and Giovanni and I are in contact, so we will let people know as soon as there's opportunity to actually be part of a clinical trial on their devices will see about engaging the Neurohacker audience in the trials.

[01:27:00] We have to wrap up here, but this whole thing Giovanni's talked about with the closed loop induction, where we're reading what the brain's doing and then feeding back to the brain what it is doing to help it do it more efficiently in coherence and synchrony. That's actually just the first of two technologies that his team has been working on.

And so just briefly, will you hint at what the second one is and [01:27:30] what it kind of offers to the field of learning?

Giovanni S.: So the second one is actually Northwest and the phase lock loop stimulation has been developed, is a leader in this field. There is a little bit older technology has been around for about 10 years now, and there are dozens and dozens of studies all around the world which show how efficient this technology is. It's called [01:28:00] target memory reactivation.

So there has been after a long, long time, this dream that we could learn during sleep, because most people think that is a Hedo time. We already show that it's not at all. There are a lot of things happening during sleep, but most people think, "I'm losing eight hours would be nice if I could use this time to do something, right, like maybe learning something."

So people end up being, you know, there is a professor. His name is Ken Paller. [01:28:30] He's one of the leaders of his field of a target memory reactivation, and he has this presentation where he talks about the history and how people had interesting inventions in the 1800s where [inaudible 01:28:44] could learn all kind of different things during sleep, right? But it's a legend. It's a myth, but it's not true.

There have been experiments where people try to input information during sleep. Now, there have been some recent ... I read some recent papers. I [01:29:00] need to understand it better, but it seems that there are some thing that you can do to transfer some information during sleep, but in general, if you just play a tape of it tells, you know, like anatomical parts or a language, you know, you try to learn Chinese while you are sleeping, it's not going to work. People have tried. It doesn't work, at least, in the more straightforward way, just playing some Chinese words [01:29:30] with an English translation, and you do it during night, it's not going to work.

What works is if you make an association between learning [inaudible 01:29:41]. So Ken Pallor did this famous experiment where people are there to learn, they had a grid, and the had to learn the position of an object in this grid.

So for example, I show you a little picture of a cat. Imagine you have a grid like an Excel spreadsheet, right? And I'm going to put the [01:30:00] cat on B2, right? Or I'm going to put a peacock in C3, and I show you an example of how everything is organized, and while you're learning, I'm playing a sound. So for example, while I'm moving my cat to an example that is a show on the left side of a screen, I have to reproduce every position of each single object in this grid, I play a sound. So when I'm moving to its right location [01:30:30] the little picture of a cat, I'm playing meow, right? When I'm moving the talk, I'm playing the whistle of a teapot.

I'm associating almost like in a Pavlov dog kind of fashion, a sound and an experience, in this case, the position of these objects, and the idea is that maybe I have 50 of these objects, and at night, during slow-wave sleep, when [01:31:00] there is this consolidation of memories, when the brain basically selecting what to keep and what to throw away and how to trans ... It's transforming short-term memory to long-term memory is this process we already mentioned is called consolidation.

During sleep, I'm playing the sounds. So I will play the meow sound. What happens is that because of this association, the entire ... So basically, our memory are encoded in the brain is a network, right, is neurons that are firing [01:31:30] together in a certain pattern. So neuron number one will fire now, neuron number two will fire a little bit later, and neuron number three will fire a little bit later. So these are firing this sequence is actually what we call a memory. This is what the memory is.

And so because there was an association of a sound with the rest of the memory that was the position of the object, the object and its location in space, my brain is associating all these things. So if I play part [01:32:00] of this network of memories, like in this case, the sound, everything else would be reactivated during sleep.

So the brain prioritize this memory versus anything else, though I had other experiences. I met a friend at lunch. Instead of remembering specifically that memory will emphasize this useful memory, like, let's say in this case was an experiments and wasn't all that useful where I put this [01:32:30] cat, but let's say I want to learn a language, I want to learn an anatomical part of studying anatomy, I want to learn the name of a bone or whatever, I can play a sound when learning and then play that sound back during sleep, during slow-wave sleep.

Daniel S.: So this is-

Giovanni S.: What that shows, it's enhancing that memory. So when they did the experiment, they choose 25 of these object at random to play the sounds during slow-wave sleep, and then they tested how people performed [01:33:00] in remembering where the location of these objects, and the object that were played at night were remembered much, much better, but by a big amount.

Daniel S.: So increased rate of learning via memory prioritization during the memory consolidation process via this kind of auditory Pavlovian conditioning?

Giovanni S.: Correct.

Daniel S.: Now can these two technologies be used together? Can we be increasing the amplitude of delta sleep so that [01:33:30] you'll be ... You have more net bandwidth to remember everything, and then increasing the prioritization towards the areas one actively is trying to learn?

Giovanni S.: Right, so there are two things that you can benefit by combining the two technologies. One is it turns out, so for example, remember ... We say we amplify the ability of the brain to remember in general, so if you amplify that ability and at the same time, you target some specific memories, the two technologies [01:34:00] combined will be much more efficient than alone.

So [TNR 01:34:04] works by itself. PLL works by itself, but if you combine the two now, you have an enhancement in the ability of the brain to remember and doing this consolidation process, and you can also target some specific [inaudible 01:34:17] experience that you [crosstalk 01:34:19].

Daniel S.: So how long till the listeners that are all excited about this can actually be sleeping with these devices on?

Giovanni S.: We hope to have at least the phase lock [01:34:30] loop product within, I would say, six, seven months from now. In fact, we are actually now planning to do a Kickstarter company, so be on the [inaudible 01:34:44] for that, so probably in the next months, we are getting up for a Kickstarter company, and we will have a prototype that can show our supporters at the time and some nice CAD [01:35:00] design to show how the final product will look like, and we hope to be in productions about maybe six to one year from now.

Daniel S.: Awesome.

Giovanni S.: It depends on some of our partnerships and some of our [inaudible 01:35:16], so they are, I can say this without revealing too much, there are some big players that are very interested. Some of the big names of people associated with the technologies, they are very, very interested in this field, and [01:35:30] they talk to us about possible partnerships. So if we have the kind of support maybe could be much faster to go to production.

Daniel S.: So for the listeners in closing, for now, put a white noise machine in your room, if you have ambient noise, to try and decrease disturbances, auditory disturbances from sleep. And then stay apprised to this technology. When the [01:36:00] Kickstarter comes, I'll be on it, and if you happen to have scientific, technological, or industrial design or funding resources and are interested, either go to Giovanni's website, deepwave.tech, contact them or contact us, and we'll put you in contact. Contact us at Neurohacker Collective support, because we're in regular contact, and Giovanni, this has been a fun podcast. [01:36:30] I appreciated getting just the tiniest little essence of your work out to people, because I really believe in it, and I want to see it have a lot of success soon, and I want to be using the tech soon.

Giovanni S.: Thank you. Thank you for your time and your very good questions.

Daniel S.: All right. More soon. Thanks all.

Giovanni S.: Right.

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