[00:00:00] Speaker A: Welcome to the Heart Rate Variability Podcast. Each week we talk about heart rate variability and how it can be used to improve your overall health and wellness.
Please consider the information in this podcast for your informational use and not medical advice. Please see your medical provider to apply any of the strategies outlined in this episode. Heart Rate Variability Podcast is a production of Optimal LLC and Optimal HRV. Check us out at optimalhrv.com Please enjoy the show.
Welcome friends to the Heart Rate Variability Podcast. I'm Matt Bennett. I'm back here today with Dr. Ina Hazan and a very special guest, Dr. Mara Mathers, who I met at AAPB conference last year. Just another plug for the next year's conference which registration Ina I believe is open as of today or a few days ago.
But as we talk about on this podcast all the time, a really great opportunity for the HRV nerds out there to really connect with leaders in the field. Including last year I was able to connect with Dr. Mathers and learn about her work and her great keynote there. So Dr. Mathers, welcome to the show. I'm so excited to have you. I've wanted ever since I heard you talk. I couldn't wait to get you on the podcast and I would love I always like to start out just episodes with talking a little bit about yourself, introduction for our audience and kind of where did you learn about heart rate variability? How did that come in to your your thinking?
[00:01:49] Speaker B: Sure, yeah. So I learned about heart rate variability probably many years ago. I mean it's really swept the field of psychology in terms of being such a prominent biomarker of well being. And it's also really interesting for athletes as well of course. And I'm a runner as a hobby and a biker, so all these things interest me.
And we started collecting heart rate data from our participants. We do a lot of neuroimaging and look at the brain and how it relates to emotion.
We just measured average levels of heart rate variability in our participants and looked at what this related to in the brain. We started finding that heart rate variability was really strongly related to emotion related circuits. So for instance there's the amygdala. You've probably heard about it. It's a popular brain region to talk about in the news because it's a very important emotion center.
The amygdala has activity that's coordinated with the prefrontal cortex. The prefrontal cortex controls a lot of our behavior and it's thought thought about as doing executive function and so forth. And you can look when people are just resting at how coordinated activity is in the amygdala and the prefrontal cortex. And we found that for both older and younger adults, activity in the amygdala and prefrontal cortex was more coordinated in those who had higher heart rate variability.
Then we also looked at brain structure and how that relates to heart rate variability. And we found that the left orbital, orbital frontal cortex was larger and was thicker in people who had higher heart rate variability. And this also was true across younger and older adults.
These regions are really important for emotion regulation.
Of course, in the field of psychology, there's lots of correlations between heart rate variability and emotion.
But the way that it had been thought about at this point was that heart rate variability is like a readout on a dial of how your regulatory systems are doing.
So those same prefrontal systems that are controlling your emotions, that are helping you just not, you know, completely flail out of control when you get upset with someone, not, say, the first thing that comes to mind when you're feeling emotional or. Or, you know, trying to cheer yourself up when you're feeling down. All of these sort of processes are coordinated by prefrontal cortex regions, and those same regions also help coordinate our internal states of our bodies.
So heart rate, of course, is one very important internal state of the body, and it is coordinated in part by circuits that the prefrontal cortex modulates.
So if heart rate variability, if those prefrontal regulatory systems are doing well, your emotion should be good and your heart rate should be good, because those systems are responsible for both things. So this is the way the field was thinking about it. Like, your heart rate variability is a readout of how well these systems are working.
But I was interested in whether there might be more to the story. Could it be that heart rate variability actually in itself plays a causal role in how well these brain circuits work?
Here, need to unpack a little bit of what heart rate variability is, which, for those people who listen regularly to this, podcasts probably know a lot about it. But it's. I feel like heart rate variability is a misnomer. Heart rate variability makes people think that this is a measure of noisiness, of variability, of randomness.
But the signal that is really associated with good emotional well being is not random noise. It is fundamentally the thing that drives the signal is how much your heart rate is responding to your breathing.
So when you breathe in, your heart rate accelerates, and when you breathe out, it slows down.
And this is for many reasons, one of which is that the traffic on the vagus nerve, which controls your heart rate and keeps it lower than your intrinsic heart rate, your pacemaker cells would want it to go, which is really fascinating. If you take a heart out of the body, it keeps beating. There's pacemaker cells, and those pacemaker cells want your heart to go at around 100 beats per minute. But you know, your resting heart rate is lower than that most people. And the reason is that your vagus nerve, that parasympathetic system, is keeping the brakes on the heart.
And those brakes can be lifted very quickly as needed. So when you breathe in, that brake gets lifted a little bit. So if you have a strong break on your heart, you'll see a large oscillation in your heart rate as you're breathing.
And so people use this as a metric. And that is the primary aspect, the primary variability in heart rate that's associated with being happier, being less depressed, being less anxious, being younger, being more fit, all of these things.
So that is important just to understand, okay, when we're thinking about how all these dynamics relate to each other, what we're thinking about really is heart rate oscillations, not just heart rate variability.
And if you have a brain system that's monitoring the body, those heart rate oscillations are going to trigger the need to try to regulate, right? So if heart rate's going up and then going down the body, the brain is going to respond and say, oh, okay, I need to respond and try to bring heart rate back down.
Blood pressure is also oscillating with these breathing rhythms.
All of these things are leading these feedback loops to respond. And my thinking was, well, this might be a little bit like a workout. So if you are in a session where you are breathing slowly and your heart rate is oscillating with a large amplitude, your making these feedback loops that respond to physiology go through their whole routine over and over again.
And so this was when I submitted a grant to the National Institute of Health to do a clinical trial where people would be doing slow paced breathing, which is a way to make those oscillations very large.
Just while people are doing that, they can have oscillations from say 60 beats to 80 beats each breathing cycle that, you know, more likely might be 60 to 70 or something like that.
So these can be pretty large oscillations and people feel relaxed.
And presumably these brain circuits should be getting a workout. So what we proposed was to have people come in, have a brain scan while they're just resting quietly.
Also in the scanner do an emotion regulation task, so look at some emotional pictures and try to regulate their emotional responses to these pictures and also do a number of other tasks and measures.
We also drew blood, which I can talk about later, and we then had them go home and practice slow paced breathing and heart rate variability biofeedback for four to five weeks. That was the active group or the, the target group. But we were very concerned about the control group because as a psychologist, you know that you can have people come in and they think you want something to happen to them or you think that something's going to happen to them, and so they sort of do it.
So we wanted to make sure that there was a control group who was equally busy, equally invested, and also thought this would be something beneficial for them.
So what we told people is that we were interested in emotion regulation and how control of heart rate might be an important part of why meditative practices actually enhance emotion.
So we told one group, the group I just told you about that went home and did slow paced breathing. We told them that some meditative practices lead to these oscillations in heart rate.
And that's true.
We had a comparison group that we also did heart rate variability biofeedback with. But their goal was to try to keep their heart rate steady.
And we told them that some meditative practices lead to a more steady heart rate, which is also true.
What I've learned over the years is that meditative practices vary immensely in what they do to the physiology. And there are so many different flavors of meditation and they do very different things, which I think many of them are very useful in many different ways.
So what we've learned from our research is that the typical mindfulness focused type of meditation leads to a quieter, less variable heart rate.
But, you know, not all of them. But I'll. I can talk about that later too.
So we had these two groups of participants. At the end, we asked them, you know, how much they thought it would help them, how much they thought the researchers thought that this practice would help them, how much they liked it, how much they thought they'd keep doing it. And the two groups didn't differ in all these things. So it was a really good control group for us. Yeah.
And they came back, everybody came back five weeks later and went through another scan and did the same things again. They laid there, rested. We measured their breathing so we could make sure that the two groups weren't breathing differently during the scan. So it wasn't about our measures, weren't about what's Happening during the practice. It's how much has the practice changed something about you, in particular your brain. And we then looked at how the brain changed in rest and also during emotion regulation and we also looked at blood samples that I can tell you about. So lots of really interesting things. I can keep talking or you can.
[00:13:37] Speaker C: Direct me if I have to say. The way you control this study is absolutely brilliant. Control groups in biofeedback are so difficult.
Many people have tried doing like neurofeedback as a control for HRV which has its issues or EMG to control. Again, none of that works really well. Your control group is just brilliant.
Whenever I talk about your studies, I get into my little nerdy part and talk about how great this control is. It gives us just a brilliant way of actually establishing what HRV does out and all the potential confounding variables. So I'm very glad to hear about it from, from you.
[00:14:32] Speaker A: And I would love to you, you mentioned the blood draws a couple times. So, so I, I would love for you to continue and, and bring that, you know, we're talking about the brain, we're talking about the heart.
I, I'd love to like biochemically. What were you also looking for with the blood draws?
[00:14:52] Speaker B: Okay, so let me just give a teaser now for that, which is that I thought that this process of slow paced breathing and these oscillatory dynamics could be influencing some of the very early phases of Alzheimer's disease, sort of the preceding things that happen. So let me get back to that. This is just a teaser for that because on what I was talking about before, I should follow up and just tell you what the main outcomes were that we were looking for, which were we were interested in these emotion regulation networks and in particular amygdala functional connectivity with the prefrontal cortex.
We found that those who had been doing the slow paced breathing and heart rate variability biofeedback for four for five weeks, they showed at rest when they were no longer, they weren't doing the paced breathing at rest compared to the other group. They showed greater functional connectivity with the amygdala, in particular the left amygdala I believe. And they also showed in general the emotion networks showed greater coordination just at rest. They were more likely to be brain regions associated with emotion were more likely to be showing coordinated activity within these networks after the intervention than before.
Those were the resting measures. So it looks like we had some sort of impact on these networks that respond to the internal state of the body, but are also important for Emotion and regulating emotion.
We also had this emotion regulation task in the scanner where we showed people pictures and asked them to either try to downregulate or upregulate their emotional response to the pictures.
In the downregulation condition, we found that people showed less activity when they were trying to downregulate their emotions in brain regions that are sensing the internal sensations in, in the body.
So somatosensory sort of brain regions.
So, and that was just in the group that was doing the trying to increase their heart rate oscillations. The other group showed no changes in either the resting networks or the emotion regulation brain activity. But the group that had been trying to increase their slow paced breathing showed increases on both of these measures. In terms of the emotion regulation, it's actually a decrease in the brain regions that are responding to these emotional pictures. When you look at an emotional picture, what's going to make you feel something is you're mirroring the emotion of the person and sort of feeling it in your own body in the way that you imagine you would feel it if you were experiencing it. So it makes a lot of sense that you're sort of dialing down the activity in these brain regions that are responsible for sensation and feeling.
So those were the emotion findings. I don't know if you have questions on those, I can then move on to the other.
[00:18:29] Speaker A: I mean, there's something that, I don't know why it's kind of hitting me now. I'd love to get your feedback on this as well as you're talking about this.
The connection between the heart, the brain, the emotional regulation centers, prefrontal cortex, amygdala connections. I wonder if you have any thoughts on evolutionarily, why did we develop this skill that if we hit this certain pace of breathing, our system sort of would all sync up in a very positive way?
I just find it fascinating that we kind of hold this key inside of our biology that really allows, whether it's our athletic performance, whether it's cognitive performance, whether it's emotional regulation that really allows us to in some ways be our best, but we kind of have to intentionally change our breathing. And I'm just curious, is there any speculation from either of you, like, why did human beings develop this amazing superpower that you know, you know, scientists like both of you are kind of tapping into in very powerful ways? I just, I wonder. And if it's just speculation, I always allow that on, on the podcast. So.
[00:19:55] Speaker B: I don't know, you know, if.
[00:19:56] Speaker C: You have, well, the, the Thought that I, I had without, without having this before was, you know, this may be the way that we're supposed to function, but in our, in our human imperfection, you know, our circuits get somewhat dysregulated and we need to actually find that key to bring them back into regulation. Maybe, you know, evolution did design this really well functioning mechanism and we just can't maintain it because we are imperfect human beings. But that's all I have.
[00:20:30] Speaker A: Yeah.
[00:20:31] Speaker B: Well, I think it's just amazing that breathing is like a portal to our physiology. So we have these physiological rhythms. So for instance, there's the, what's called the barrel reflex, the blood pressure feedback system.
And it seems that there's a fixed delay that as vessels get stretched, there are these sensors that send messages to the brainstem, and the brainstem sends messages back via both the sympathetic and the parasympathetic system that deal with this.
If your blood pressure is going up, your vessels are getting stretched, these mechanical receptors sense it, and the sympathetic system gets shut down so that it's no longer constricting as much so that things can dilate more. And the parasympathetic system gets amped up so that the heart rate will go down and there won't be as much blood going into. But this is all on a fixed delay and it oscillates and it's at around 0.1 hertz, or 10 seconds, which is this sort of believed to be beautiful place to breathe at, where you're going to be affecting both the baroreflex, you and having these large oscillations in heart rate.
We have these systems that have these oscillatory dynamics that we can't really modify. But breathing we can modify. We can do what we want, we can speed it up, we can slow it down.
And so it's almost like we can pick out the tune or the chord and sort of amplify it with breathing at that particular rhythm.
And it's this portal into our physiology that, you know, various traditions have accessed over the millennia, like, of course, yogic breathing.
And apparently Italian physiologists measured people chanting the rosary. And that's a 10 second rhythm as well.
[00:22:38] Speaker A: Fascinating.
[00:22:39] Speaker B: Yeah. So it seems that, you know, there are many traditions that have known about this and, you know, access it to help people calm down and be relaxed.
[00:22:53] Speaker A: I love that. And I know some of our listeners will want to know because I always find it powerful. And sometimes I talk to researchers as well that are like, you know, the question of how long do you need to practice to be able to major biological changes.
You know, is it, is it a four week study long enough to see it? Obviously you're getting results that you can measure in a five week biofeedback practice. I'm just curious because I know the audience will be as well. What was the frequency, the time of daily practice? I'd love to know to get those results.
I'm sure you had better adherence from some people than other people. If you found a way to make everybody practice 20 minutes a day, please share that with the rest of the world that wants to know how to make people do that. But I'm just curious about the regimen that you use to get those very tangible results.
[00:23:56] Speaker B: Yeah, so we had very little variability. Our participants were amazing.
[00:24:02] Speaker A: That's awesome.
[00:24:03] Speaker B: The older participants, we had older and younger participants. The participants who are between age 55 and 80, they practiced more than what we asked them to do on average.
So we were, the first week people started with two 10 minute practices, then it was week two, it was two 15 minute, then two 20 minute practices and that's where it stayed. So we were asking people to practice for 40 minutes a day, every day, no weekends off, and people did it. And the older people did more than what we asked them to do, which is not what we expected. So subsequently we've put caps on practice to avoid that. But we get really good adherence and we put a lot of effort into that too. And I think the primary reason we get such good adherence is because we developed our own software platform.
The participants wear a sensor on the ear and those data get uploaded to the cloud and we immediately know if they've done their practice or not at certain times of day. If they haven't done their practice, we send them a friendly text and say, oh, this is the time for you to practice. And that I think is the number one reason we have such great adherence is that people just forget they're busy. It's hard to remember. If we can help them remember, then that is much better. I mean, we also did have small rewards, so people got an extra dollar if they were, you know, they practiced regularly or if they had high scores on their biofeedback, things like that. But I think the, you know, reminding people is, yeah, is number one because we've also done studies where there's been no rewards and just people get really great adherence.
So what, what that means is that we have no variability.
So we don't know whether you have to do that much to get these results. We don't know. What we do know is that we, like I said, we have been interested in meditation and how slow paced breathing relates to meditation. So we also did a study where participants did a mindful meditation practice.
We played them a recording where we asked them to mindfully attend to their breath. So a very sort of standard mindfulness meditation script. You know, focus on the sensation of breath in your belly, focus on that. If your thoughts wander, return them to your breath, those sort of instructions.
And we had one group that we asked to do that and then we had another group that we asked to do that. Plus we asked them, we just gave them an instruction to breathe in for a count of five, out for a count of five and to keep doing that.
Now originally we had started this study thinking that the mindfulness with attention to breath in the belly would make people do this slow breathing. I mean, it sounds like that's what you would do.
If you're focusing on your breath and your belly, you're going to breathe more slowly.
We pilot tested extensively and with our undergraduates in the lab, sent them home. They did not do slow breathing with these mindful instructions. You know, maybe expert mindfulness meditators do, but our novices did not. And so eventually we decide, okay, that's going to be our comparison condition. Because they're not, they're not doing the slow paced breathing. We'll compare that to without slow paced breathing, without giving them instructions to do that, to a condition where they do the mindfulness plus the slow paced breathing.
We also had a condition where they didn't do anything. They just wore the sensor and played around with their phone or whatever they wanted when we measured their activity.
The reason I brought this up here is because that study, we took a risk and it was only a week long. We didn't know, do we need four weeks, do we need five weeks?
We took a gamble and these participants went home and meditated for two 20 minute sessions just for one week and they came back. And in these participants, we were looking at blood samples and they showed the same blood changes that the participants in the five week study showed.
Yeah, so there's, there's some things that happen pretty rapidly with this practice.
[00:28:53] Speaker C: Do you have any sense of how long those effects would last? You know, people do this for just a week and then stop versus they continue.
[00:29:01] Speaker B: No, I don't, I mean, I don't think they would last all that long. I mean, I just think in terms of an analogy to physical fitness and how you can get out of shape pretty quickly, I don't know. But you know, those are all really important questions that would be helpful to know. I mean, what I think of this practice as being is an ongoing thing that people should do, you know.
[00:29:25] Speaker C: Absolutely.
[00:29:26] Speaker B: At least several times a week. We don't know, we don't know what the right dose is. I would love to do a dosage study, but we don't, we don't know. But that's what I think. Like physical activity, you know, you can't just do it for a week and then expect that you'll be great for years to come.
So.
[00:29:45] Speaker A: But at the same time too, it's exciting because if you start, I don't know, jogging or lifting weights, you don't see a whole lot of results right away. I mean, you see some results, but usually you're sore and you're tired and they're not that great. You may feel a little bit better. But to see some of the blood results come in just after a week of practice is pretty astounding that we're seeing some of those changes starting to happen. And as you mentioned that how much of this. It's the number one question I get from users of the app or people designing research study is what's the magic equation of how many times, what if I practice 10 minutes in the morning and 10 minutes at night? Do I need two 20 minute practices? Is 10 minutes enough? And you know, I'm assuming there's probably some individual stuff there, but I think it's the number one question in the field is how much to get to the benefit. And just hearing you start to see some of that after a week is really exciting that we start to see some of the biological changes.
[00:30:54] Speaker B: It is, it is. And it's really also great for researchers because we don't have to bring people in for as long to test what's going on. And so that's really helpful. But we also are really interested in the longer term effects. So I can tell you about the blood.
[00:31:09] Speaker A: Yes, please, please, please.
[00:31:10] Speaker B: Okay, so this is a little bit of a story. So your listeners are interested in heart rate variability. They might not know so much about Alzheimer's disease.
Let me tell you a little bit.
Alzheimer's disease I think needs to be thought about more like cardiovascular disease. We all have some of the indications of the disease in us as adults, as is the case with cardiovascular disease and things like atherosclerosis. And you know, it's basically, it's a continuum and it's not some people have the disease and some People don't. I think we need to think about Alzheimer's disease as a process, pathological process that's really, really tied to aging.
So aging increases the risk of Alzheimer's disease exponentially.
And what happens is.
So you might have heard about the amyloid hypothesis of Alzheimer's disease. It's been controversial for years because it was so hard to see clinical effects following this hypothesis. But it's starting to. They're starting to develop drugs that can remove what's called amyloid plaque in the brain and starting to see some benefits. But the basic idea is that we have these small peptides, small proteins that are amyloid beta peptides, and those are a normal byproduct of cellular activity. So you imagine your neurons are busy and they're going to release some amyloid beta into the brain, and that amyloid beta, the levels are not so high when you are age 20.
But researchers have measured in cerebral spinal fluid, which is the brain's fluid that surrounds the brain. They measure levels of amyloid beta peptide and find that longitudinally in healthy adults, it increases as people go from age 20 to 60.
The hypothesis is that either because of increased production or poorer clearance from the brain, that there's more and more of these amyloid beta peptides that in healthy young adults just get cleared out mostly during deep sleep, actually cleared out from the brain. And they aren't a problem in young people. But as they start to, these peptides start to accumulate, they start to aggregate and stick together and form this amyloid beta plaque that is one of the primary signs of Alzheimer's disease in the brain.
If we could keep levels of amyloid beta peptide lower throughout young and middle adulthood, perhaps we could postpone or even, you know, eliminate the possibility of getting Alzheimer's disease, which is this very slow moving process. So if you can slow it down, you should ideally not experience it before you die. Right. You'll have other issues that get you first.
So the reason that I was inspired to look at this biological pathway in with heart rate variability biofeedback is because it's been known that deep sleep is particularly important for clearing out brain waste and amyloid beta.
And deep sleep is a time of slow oscillations in the brain.
It also is a time of low sympathetic activity, low noradrenaline in the brain. Noradrenaline is the signature of sympathetic activity, the fight or flight system, and higher parasympathetic activity.
So, and this brain clearance system is a very interesting one that really has only come to light in the last 10, 15 years. And it's called the glymphatic system.
And it's really fascinating. There are of course, arteries that go into the brain and veins that come out and around those arteries is. So you've got the, the channel of the artery, the tube, and you've got another container around it that has fluid in it. And that fluid is cerebral spinal fluid. And the outer wall of that wrapping around container are these glial cells that have water channels.
So the artery is pulsating with your heart rate and it's oscillating with your blood pressure oscillations and your oscillations in blood pressure and respiratory oscillations, all making your arteries oscillate.
And those movements propel the cerebral spinal fluid to also move.
And when it flows out of those water channels into the water filled spaces between neurons, there's a directional flow and it takes waste with it.
And that waste, that CSF that's now mixed with the waste, then flows into the channels that are around the veins and flows out of the brain and gets disposed of through your body waste disposal systems.
So interestingly, that fluid in between your brain cells, there's more volume for it when you're asleep.
Researchers have measured what's the volume of this fluid in animals, not in people, and they find that it's greater during sleep, which suggests that the brain cells or the cells are shrinking during sleep so that there's more room for the fluid. And researchers have given animals a cocktail of noradrenergic drugs that increase noradrenaline, which, as I said, is the primary neurotransmitter of the sympathetic system. And when that happens, the fluid filled spaces shrink. So when you're awake, it seems that your brain cells are a little bit larger, making it more difficult for waste to be flowing out. And it makes sense that cells could be, the size of cells could be influenced by their activity, because of course, you know, sodium is a key part of action potentials. Other ions are important too, and they influence how much water is retained and those sort of things.
So anyway, we have these really interesting physical properties that change during sleep and might change during, say, a 20 minute slow breathing practice. So that was the hypothesis that we might be able to mimic some of the features of deep sleep and in particular the low noradrenaline and the oscillatory dynamics of csf, slow oscillations that would enhance waste clearance. That is really problematic in aging. So in older adults, they don't get as much deep sleep and the amount of slow wave activity during sleep is correlated with Alzheimer's disease pathology.
So it's very important, very important to get your waist cleared out, to have this time of deep sleep. And it declines a lot in aging. So could we sort of supplement it with a day time session of slow paced breathing? So that was the idea. And so we, we took blood samples because you can measure plasma, amyloid beta.
When some of these amyloid beta are cleared out of the brain, they move to plasma. Also a lot of the amyloid beta and plasma is just produced in plasma as well. So, so there's a whole sort of parallel system of amyloid beta production in the blood circulatory system and in the brain. And the platelet cells actually produce some of this amyloid beta.
So that was the motivation and you know, for clearance. There's a particular signature of amyloid beta that you would look for in plasma, which is that there's more amyloid beta 42 then amyloid beta 40.
And this ratio, it has turned out to be sensitive and correlated with the pathology of amyloid beta in the brain. And the reasoning is that amyloid beta 42 is a little bit longer, it's a little bit more sticky than amyloid beta 40. And so it seems to be more likely to be left behind in the brain and, and stuck as amyloid plaque. And when that happens, then the ratio of amyloid beta 40 to 42 both in CSF and in blood goes down. And that's a bad thing.
So what we did find, we found just on the edge of significance, not quite significant effect for our older adults, that the slow paced breathing did increase this ratio score, which is a good thing.
[00:41:22] Speaker C: Wow.
[00:41:23] Speaker B: So that's great.
It might, we still need to do more studies with older adults to see if it does improve clearance. But the large signal that we got was actually a little bit of a surprise, which is that Both amyloid beta 40 and 42 significantly decreased in the group that was doing heart rate variability biofeedback to increase their oscillations. So the slow paced breathing group and significantly increased in the other group.
So yeah, we had this active control group that in our emotion outcomes showed no effect. Right. There was no difference. But in these blood samples they showed a clear effect, sort of the mirror image of the other group.
And so we were very excited because this was a large effect size difference between conditions. It was seen in both younger and older adults. So we had an internal replication in our study and it should, potentially it could matter, which is as I Told you. From age 20 to 60, we see increases in amyloid beta peptide just in general. And so it seems that through adulthood, for whatever reason, we seem to be producing more amyloid beta peptides. And that might be part of this problem, why we end up with aggregation and amyloid beta plaque. So if we could lower that, sort of slow people down by a few years on that trajectory of amyloid beta, that might slow down the disease. And so those effect, those large effects of the breathing, heart rate variability, biofeedback and breathing conditions on plasma amyloid beta, we also saw in the meditation study. So the meditation study had the group that was doing mindful attention to their breath without doing slow breathing and the mindful attention to their breath with slow breathing. And those two groups showed again this opposite pattern. So doing mindfulness alone is increased plasma amyloid beta. Doing mindfulness plus slow breathing decreased it. Now you might be like, why? Why would mindfulness increase?
So I don't know if any of, if either of you have tried mindful meditation, but it is really hard. It's a serious challenge. It's very attention demanding. Your thoughts constantly wander, especially if you're a beginner.
And that all of that focused attention is very much a norgic process, right? So, so the brain needs noradrenaline in order to focus attention. It's very involved in that. So if noradrenaline is your fight or flight, get up and go focused attention, sort of neuromodulator, and you're increasing it every day in your meditative practice, then you might be increasing this byproduct of cellular activity.
And that's not necessarily a bad thing, right? I mean, we need to practice focused attention. It's very important. Like noradrenaline is very important for us. It does all sorts of good things.
I don't want to knock noradrenaline. You know, it's what our lab studies. It's one of our primary focus, you know, foci of our work.
And it's really great for memory, learning new things, reshaping the brain. It's very important.
But the issue is that in order to be have your brain in good shape, you also need the parasympathetic time in the day. You need that deep sleep to clear out the waste that your brain exercise has done. You know, all that focused attention and noradrenaline. And so it seems like, you know, like I said earlier, there's all sorts of meditative practices that have different benefits and different physiological outcomes. And right now, from what we can see, it seems like at least in novices, doing mindful meditation is really training focused attention and is good for that. But it is also perhaps initiating these physiological pathways that involve noradrenaline and might be increasing this metabolic waste product which is amyloid beta.
[00:46:06] Speaker C: What a great argument for combining mindfulness and HRE biofeedback together.
You get the best of both worlds without the potential side effect.
[00:46:18] Speaker B: Yeah, yeah. I mean I, I think it's like exercise. I mean we really need to go out there and you know, if you're, if you're into physical fitness, you know, doing high intensity training, interval training is really great.
It's, you know, certainly hard on the body, but pushing things is important, but you also need that rest.
[00:46:38] Speaker A: Yeah.
[00:46:38] Speaker B: So, so just I feel like our bodies are set up in this way. You know, we need both of these types of activity and as we age it's pretty ironic because the system that just collapses is the rest and digest system.
So it's a massive, massive change.
There's data from 8 million Fitbit users that show that heart rate variability, they estimate heart rate variability declines by 80% between age 20 and 60.
So huge, huge change is happening in early adulthood and midlife and we know very little about this. And this is something I think is really important for us as researchers to focus on.
[00:47:29] Speaker A: I love that. I'm curious, did you find in your research as you're doing this research, had anybody studied long term mindfulness practitioners like you study novices to see if there was any difference in a novice versus a somebody who's been practicing for a year or five years?
Was there any of that data available out there?
[00:47:57] Speaker B: So you know, when I started studying heart rate variability biofeedback, I thought it was fascinating. I thought, oh, this is really the, the route through which probably a lot of meditative practices get their benefits is slow breathing. Yeah. And so I started like checking out different meditative practices and every. I went on a 10 day silent Vipassana retreat. I took what other. Yeah, I took like mindfulness classes also. Another.
I always blank on what it, what it's called, but every time I took classes I was just completely surprised at how wrong I'd been about what that meditative practice was doing. Physiologically. I was just totally off base in just when I just read about it.
And so Vipassana was very interesting.
They, in this particular retreat center, they had us spend the first day mostly focusing on our upper lip and the sensation of breathing at the nostrils.
And they call this Anapana.
And I'm in there. And I think, you know, I'm going to be doing my slow breathing and I realize, like, in order to focus on the tiniest sensation of, you know, like the little hair follicles and how they're, they're feeling tickled by the breath.
Your breath almost stops. I mean, it's incredibly quiet when you're doing that practice this focused, mindful attention to sensation.
[00:49:31] Speaker A: Yeah.
[00:49:32] Speaker B: At the, you know, target right at the nostril.
And everyone in the room super quiet. And then I went and found in the literature that they had found that people, experts practicing anapana show lower heart rate variability.
Then at rest. Then at rest. Wow. So even experts, you can get certain types of practices. So that, that was the practice I thought we were going to use as our control was to have people focus on their upper L versus people focusing on their belly. And I thought the people, you know, focusing on their belly would do the slow breathing, but they didn't either. So.
So just to make things really clean, we had both groups do the, the belly breathing. So.
So yeah, I, I think that.
And it's just like there's, you have to go experience, I think these meditative practices to really understand what, what they are and what they're doing.
[00:50:32] Speaker A: I love that. Another question, I wanted to ask you this at aapb, but I figured you wanted time to relax after the keynote. But with your findings.
I mean, my mind jumps to. And I'm not hearing you say this, but it's just what HRV biofeedback as a preventative thing for Alzheimer's a possibility in your stuff? I mean, we. More research needs to be done. Are we also talking about. Because I always think with Alzheimer's and I'm a novice, that I'm not claiming any expertise is that plaque gets stuck, like the plaque's not moving.
Is there a potential of, you know, getting, for lack of a better word, HRV biofeedback being treatment as well? Are we able to clear out some of that sticky stuff that is. Is causing the symptoms of the horrific symptoms of, of this disease?
[00:51:38] Speaker B: Yeah, we don't know.
And I should say the really important next step, step for our research is to collect cerebral spinal fluid before and after a few weeks of the practice. So right now we, we're. We have these large effects in plasma, but we really need to see if a parallel process is happening in the brain. I think it will because platelets have a very parallel process of producing amyloid beta as neurons do. But it remains to be seen. And so we've been writing proposals and trying to get the funding together to do this pretty intensive study where we measure cerebral spinal fluid before and after.
But to your question of whether this could be a treatment, I'm not so optimistic about that. It's possible.
It's possible it could help, but there's challenges a lot of ways. One challenge is that presumably to get the benefit of the practice, you have to be in good enough physiological shape that your breathing makes your heart rate oscillate. Yeah. And that power of breathing declines with age.
And so, you know, we, we see that, you know, in, in healthy adults age 55 to 80, we see effects of the practice on plasma amyloid beta. They aren't as large as the effects in the younger. So the younger show larger percent changes than the older. So.
Okay, you know, I think we have that limitation and. Yeah.
What. Whether it could help clearance? It's possible, it's possible, but I would expect the, that it would be more subtle and not a dramatic thing. But that's just me. I don't know. We really have no idea at this point.
[00:53:41] Speaker C: So this sounds like a really great practice to instill in young people so they continue with it and potentially, you know, prevent, you know, or at least delay the onset of Alzheimer's.
[00:53:53] Speaker B: Yeah, yeah.
[00:53:54] Speaker A: Thinking about it and building up that skill in some ways during your 20s, 30s, 40s, getting that out and then I'm assuming it might be easier, you know, as you get old. Like I do like that I've got this skill build up that hopefully can continue to produce even if the benefits have lessened some extent for the next 20 years.
I can take this skill into hopefully maintaining, you know, doing maintenance, if nothing else to this. But I just find it such a excite the doors that you open through this research, especially knowing the devastating effects of Alzheimer's and how we haven't really found great medication options.
I mean that's where I just got goosebumps listening to your keynote like this has such promise to this. So I've got my fingers crossed that those studies, the follow up studies will be funded because I'm just. Your research is just so powerful.
Yeah. That I can't wait to see where it takes you.
[00:55:04] Speaker B: Yeah, we're really excited. I mean it has potential to be really important.
We have a lot of work to do to show, you know, does it really affect this pathway? Does. What are the long term effects?
Is it affecting amyloid beta in the brain? You know, all of these things. But from what we know about the physiological systems and you know how dramatically the sympathetic system gets hyperactive in aging and the parasympathetic system sort of crashes and burns. And if we could even out that imbalance, at least somewhat, there's a lot of things we might be able to benefit.
[00:55:52] Speaker A: I love that.
What I love about doing the podcast and talking to folks like you is the questions that we don't have answers to. We always hit those. Almost every episode is. But what I love about the work that you and others are doing is if you didn't open that door, that wall would be closer to us. The fact that you opened the door for. Okay, speculation for the next question. The next study is what I love about this field because we are far from having, I think, a fraction of the answers to the power of HRV biofeedback and the fact that you got the blood results, I just like said, yeah, we got more questions, we hit that wall. But you got us so much further and asking, I think, the right questions next. So I just want to, I just want to thank you for your work because it was some of the most exciting. I've looked at tons of HRV studies and some give me goosebumps, others not so much. And yours was like caught me on fire for the potential of what your findings were pointing to. So thank you so much.
[00:57:01] Speaker B: Oh, thank you. Well, it's been fun talking to you. Thanks.
[00:57:04] Speaker A: And Dr. Mather, thank you so much. We'll put some links to these articles, a little bit about you in the show. Notes that everybody can always
[email protected] with that, you know, always a pleasure. I wish this conversation could go on for another three hours, but that's my kind way, Dr. Mather, of inviting you back to talk about future research or just nerding out about whatever you want to about hrv. So thank you so much for your research in. As always, it's a pleasure. And we'll see everybody next week. Thank you so much.
[00:57:42] Speaker B: Great. Thank you.
Take care.
