Exercise Physiology | Nervous System (Part 5)
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Welcome everybody to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike Todorovic, and I'm joined by my co-host, it's Jon Hamm, everybody. Famous actor from Mad Men. Wow, welcome, Jon. I just want to let the listeners know that the other day, Mike informed me that I made him uncomfortable. Yeah.

Because I violate people's personal space. I actually found this quite hurtful thing to say and it completely ruined our bath. How are you, Matt? What's been happening? Anything new? Long weekend. Oh yeah, Easter long weekend. That was good. I spent the whole Friday in your backyard. Doing? Cutting trees down. That's right, tree lopping. Matt came over with his chainsaw.

Um, which he, he nicknamed it's weird nickname. I didn't really like spray painted on the side of his chainsaw. Little Mike, it's called, which I find strange considering I'm big Mike, but, um, yeah, you chopped down a bunch of trees for me. Thank you for that. Uh, some of them were a little bit iffy. And it's interesting that he got me to cut down the poisonous ones. Yes, I did. Um, it's like, no, you don't need protective equipment. You're fine. Keep your mouth open while you're chainsawing. Um,

Yeah, I've got more to chop down. The neighbour actually asked that tree that we left because my wife said, don't chop all the trees down. My neighbour asked if I could chop that down because he said that some of the roots are going across. He said some of the roots are over 10 metres long and are going into his plumbing. So I need to chop that one down. That's a fair reason. That's a totally fair reason. Now, everyone's obviously really, really – everyone cares about that. We are talking today –

about the nervous system. And more specifically, we're talking about the role that exercise can play. Well, how the nervous system controls our body through exercise and the benefits that exercise can have

On our brain and nervous system. So it's a two-way street here. The nervous system controls movement and movement can help benefit the nervous system. And we're going to go through a fair bit of stuff, I think. We're going to go through a little bit of anatomy and physiology, a bit of a background so people understand what's going on. Set the scene, as you would say. And then we're going to talk about some of the benefits, some of the contentions.

What do you reckon? Yeah. All right. Let's start at what I think is the beginning with just organization of the nervous system. So when I think of the nervous system, I always say to my students, you've got the central nervous system and the peripheral nervous system. And the central nervous system- That's anatomical structuring. So, well, it's central anatomically and physiologically. Okay.

meaning it's central because the brain, the brain stem and spinal cord sit right in the middle of the body. So it's central anatomically. But it's also central functionally for the nervous system because this is the site of information integration. Central processing. That's right. This is where we make sense of signals. So, you

You know, I'm a smart guy and this is how I like to teach my students. But then we also have the peripheral nervous system. So these are all the nerves that shoot. That's more my area of research. It is. Yes, yes, you do. You do. And feel free to interrupt me at any point with information about your research. I was being serious there. I thought that was your typical sarcasm. No, no, just don't ever interrupt me again.

The peripheral nervous system, all the nerves that shoot out and away and back into the brain, brainstem and spinal cord. Now I'm going to ask you a question here. When it comes to the peripheral nervous system, all those nerves shooting out and away and back into the brain, brainstem and spinal cord, you can divide them many ways.

So I'm going to ask you this. There's nerves that shoot into the brain, brainstem and spinal cord. So sending information towards the brain, brainstem and spinal cord, what would you call this division of the nervous system? Simply we call it the sensory or more medical terminology sometimes is called the afferent

Division, let's say. So the way I remember it is afferent. It sounds like a ferry as in like a transport system. Yes. And that ferry is taking things away from the point of stimuli. So the A for away. Away, yes. So from the point of stimuli. Yeah, that's right. So if you are picking up touch in your fingers, that would be a type of sensory experience and that's getting projected to your spinal cord.

and then up into your brain to make sense of, to process and then percept what that was. That bringing in, that signal to bring in is an afferent signal. And so then all the nerves that are shooting out and away from the brainstem and spinal cord, what do we call that division? Efferent. So also ferries. But it's efferent. With an E, so it's going to the E vector.

So I'll use the same example. Let's just say in this case you put your hand on a hot plate so now it is not a pleasant, not non-noxious stimuli. It's now a noxious stimuli so it's now painful stimuli.

you've received the signal. It's gone. So that's afferently goes into your spinal cord, but then as efferent signal goes out to move the muscles effect, they're the effectors to move your hand away from the hot plate. Yeah. Okay. So sensory, I knew that is a reflex, so that doesn't require the brain, but it still goes into the central nervous system. So sensory in motor out afferent in efferent out. Now there's more divisions here, right? So,

You said that sensory in, that's true, but there's different types of sensory in. So what are the different types of sensory in by name? So that one I gave you, which was in your hand, you'd say that is coming from skin. So that's a somatic structure. So if you're bringing information from somatic structures such as skin, muscle,

bone, joints, you would say it's somatic. And soma means body, right? That's right. Whereas if you wanted to bring information from organs or viscera, you would use the term visceral sensory.

Or afferent, visceral. So we've got... Visceral, afferent. So we've got somatic sensory coming in and visceral sensory coming in. Yeah. And you could argue that there's one more which is special sensory. Yep. Sight, sound, smell, taste, touch, those types of things. Well, not touch, sorry, but smell, sight, taste, sound. Okay, so they're the three coming in. But in a way, I think Aristotle said this, all sensory is touch. And so you would even say visual is touch.

and taste his touch, hearing his touch because the stimuli, the force, the energy is still touching a receptor. So photons of – this is a bit of a transgression. Transgression. Going down or digression. Going down. Going down. I'd say it's a transgression as well because it's an egregious change of topic. But no, keep going.

So the photons, we're doing visual stimulus, which is special sensory. The photons that are coming from light is coming through your eyeball to the retina, but they are a type of energy which is then landing on receptors in your retina cells, which is physically touching them but changing their properties to then transduce that energy, being photon energy, into electrical energy.

Same thing with... I'm going to disagree. Same thing with hearing. Hearing is... Sound energy. Sound energy, which is in waves. Yeah, which doesn't touch anything. It does. When it gets into your cochlea, it projects through movement or displacement of the lymph within your cochlea, which then displaces the hair cells.

And you'd call that touch? Well, I wouldn't really, but it is a mechanical change. Okay, that's what then you could argue that they're all... You could say molecularly it's touching. Yeah, okay, maybe. Look, it's a bit of a stretch, but you could make that argument if you really wanted to. Let me make the argument that if you really want to get down to it, nothing ever touches anything because everything is the electron orbits repelling each other.

And that's... So you could argue that Aristotle was wrong and so were you in that nothing touches anything. Yeah, that's true. All right. God, digression. Let's talk about the efferent. These are things coming out, signals coming out. They're motor signals coming out. Oh, okay. So...

That's afferent done. Yeah. Now we're going efferent. Yeah. I said that. So let's do efferent. These are the motor signals coming out. What are they? What are the different divisions for the motor? Somatic again. Yep. So that's generally moving things that you have conscious control over to some degree. And that would be skeletal muscles. Cool. Cool. And what else? And then you have viscera. So you would say this would be visceral efferent.

And that is generally then termed the autonomic nervous system. But when you say visceral efferent or efferent, you mean that telling organs and glands to secrete substances to change their diameter or to potentially move. Yes. So this could be the heart, the respiratory tract, the digestive tract, the secretions of these tracts. Mm-hmm.

urinary genital tract and so forth. And so you're saying that this is the visceral motor division, but we also call it the autonomic division because it happens automatically. We don't think about it consciously, but we have another name for the autonomic. It's got two subdivisions. So, you know, people freak out, but these two subdivisions are very important when it comes to the role of the nervous system in exercise physiology. So what are these two divisions?

Sympathetic, which is colloquially known as the fight and flight. And then you have the parasympathetic, which is colloquially known as the rest and digest. And just very generally, what are their jobs?

Fight and flight is kind of to keep you alive in stressful situations and the parasympathetic is what your body's trying to homeostatically regulate when you're at rest. So you could make an argument that sympathetic because it's trying to...

keep you alive during times of stress, and we've made an argument before that exercise is a stressor, that the sympathetic nervous system is most active during exercise compared to the parasympathetic. Yeah, yeah, you could make that argument. However, what we'll probably get into later today when we look at exercise effect on the nervous system, you might actually find that by performing exercise more frequently, you actually decrease the sympathetic tone

at a more common, what's the word, all the time? At rest. At rest. So if you can then modulate that.

and not have the nervous system activated as frequently, it could have beneficial downstream effects on the cardiovascular system, for instance. But what we also find is that the sympathetic also becomes more efficient during those times of exercise. And so it's great at increasing heart rate, changing the diameter of your respiratory tract, blood vessels and so forth to aid in that exercise activity.

All right. So we've, we've done the divisions of the nervous system, sensory coming in. That makes sense. Motor coming out. That makes sense with a couple of subdivisions for each. We need to talk about the functional unit of the nervous system, which is the neuron, because we need to understand neurons to understand how the nervous system tells muscles to work and how exercise can occur. So Matt, can you tell us what the structure is of a neuron? What are the, what are the regions and areas of a neuron that people need to be aware of?

Okay, so like you said, the neuron is the functional unit of the nervous system. There's billions in our nervous system, so they're obviously a very important cell type. Generally speaking, they don't regenerate like other cells, so they are there permanently unless they're being killed off. Now, the way that they communicate amongst each other is they have projections like a tree, right?

at one end of the neuron, which we would term dendrites, and particularly in the brain, you could have dendrites that could communicate with other neurons upwards of 10,000 different connection points. So that then gives you a lot of complexity in the way that neurons communicate between each other.

Now, the broad part of the tree, so the central part of the tree you would say is the body, the cell body, which would be similar to most cells. They would have a lot of the organelles located there, like the nucleus and the mitochondria. But then the neuron kind of squeezes to this central projection, which then elongates in a kind of a cylindrical manner here.

depending on how long it wants to go for, some neurons, if you look at, say, a neuron from your lower back, so your lumbar region can go all the way down to your toes. So depending on how tall you are as a person, that could be longer than a metre in length. Yeah, so Matt's got a three metre long sciatic nerve. So if you're a giraffe, you could have neurons that...

stretch the whole length of the neck, which would be meters, right? So that one central projection of that one cell could go a long, long way. What's it called? Oh, sorry, axon. Oh, it's called an axon, okay. And this is where, if you want to simplify it, this is where that electrical impulse would be carried along that axon until it gets to the end of the axon. Now, what would you call...

Where the axon terminates, you'd call it the axon terminal. Great. Finally something easy. And this is where it communicates either with another neuron or with an effector organ. Yeah. Yeah. And in this case...

If it's going to go to those, either way, it changes its properties here for communication. No longer electrical, it then goes into a chemical form of communication, which is usually done with a neurotransmitter. Beautiful. Should we talk about how a neuron actually communicates? Briefly. Okay. Oh, that's... I mean, we don't want to make this whole podcast, you know, just about the electrical properties of a neuron. Okay. I get the hint, man. I get the hint. You just like it because this is your...

Well, I talk about this. It's not my favorite area by any means, but I do talk about it and I like physiology. So I like, and I like talking. All right. Feel free to interrupt me at any point about your research or anything like that. Even just what's been going on in your life. But no, ask questions, interrupt. The neuron, that signal that it sent, that it sends. So it needs to initiate a signal and it needs to send the signal down the axon.

and hit those axon terminals so that it can speak to whatever it is innervating, right? So that could be another neuron, it could be a muscle, or it could be a gland, for example. So let's just say that this neuron needs to be stimulated to speak to another neuron. Okay. So this neuron, what happens is this. Effectively...

Every cell in our body has embedded in its membrane something called a sodium potassium ATPase pump. Beautiful little enzyme structure that takes- And channel? Channel and enzyme? Yeah, it's definitely- Channel and pump. It's a pump. Yeah. Yeah.

It's a pump because it actively throws things against their concentration gradient using energy. So this is primary active transport. If you want to go back to the first six months of biology, primary active transport. Effectively, the sodium-potassium pump, like I said, membranes of every single cell of our body will have these, multiple, sometimes millions of them per cell.

If we're thinking about a neuron, it will take sodium and throw three sodium outside of the cell and exchange it for two potassium, throwing two potassium into the cell. Now, knowing the fact that what we have here are ions, ions have charges, right?

And when we talk about the way that a neuron sends a signal, it's not like the electrical signal that gets sent through the wires of your... Yeah, they're electrons. And these electrons get excited and play basically hot potato by exciting themselves and exciting the ones next to them. And they just do this all the way down the wire. So we don't actually send an electron down a wire when we make a telephone call. We excite one electron, which excites its neighbor, which excites its neighbor and so forth.

That's not how neurons work. So when people say we're sending electricity, it's right and it's wrong. We're sending charges. And so if we think about the neuron, the things that have charges in the body are ions, charged atoms or elements. So examples are sodium, potassium, magnesium, chloride, calcium. These sound like electrolytes. They are also known, aka electrolytes, salts, which allow for conduction to occur.

So we've got this sodium potassium pump throwing three positive sodium outside. It's got a positive charge and two positive potassium inside. If you now count the charges, we've got three positive things outside of the membrane, two positive things inside the membrane. So there's a net positive charge outside of the cell here. Great. We've just developed a charge or established both an electrical gradient and a chemical gradient.

The electrical gradient is it's positive outside, negative inside. The chemical, more sodium outside, more potassium inside. We call that the electrical chemical gradient. And every cell does this? Every single cell has this gradient created. But the thing is that there's some types of tissues called excitable tissues. Todorovic tissues. Todorovic tissues that really rely upon this gradient because...

an excitable tissue, which is predominantly neurons and muscle, they've got the capacity to do nothing like me, but if they get excited, they can just go nuts and they do what they need to do. So when you excite a neuron, it sends a signal. When you excite a muscle, it contracts. When you excite me, I annoy Matt, right? Do you know what I think of when, what comes to mind when I think of this? Yeah. Futurama.

Do you remember that robot? Coffee episode? No, that robot that's like a car salesman. Yes. And then like Fry is there to negotiate to buy a car, but then he keeps bidding to pay more instead of paying less. And every time the salesman goes back to tell him, he gets more excited and then finally explodes. That's me. That's me. I'm the robotic car salesman. So we've now established a gradient.

Now, we say that this cell membrane is polarized because there's a charge difference. Now, here's the other thing. If you were to count what the charge difference is, it's not very great. It's maybe like five millivolts different, right? So the inside is probably negative five millivolts compared to the outside. But what excitable tissues tend to have are some little channels, some doorways that are creaked open a little bit for potassium.

So if you've got a door that's creaked open for potassium and most of the potassium is inside, because remember that's where the sodium potassium pump through it,

it wants to leak outside. So we have some potassium leakage outside carrying its positive charge with it, making the outside even more positive compared to the inside. Or you could say making the inside even more negative compared to the outside. And now if you test the charge difference, the inside of this neuron is negative 70 millivolts compared to the outside. And that's what we call the resting membrane potential.

All right, so that's an interesting point because we know that, going back to electrolytes, that potassium has a profound effect with excitable tissue. So if you were to, let's say, consume high amounts of potassium or you just had high amounts of potassium in your extracellular fluid, this would then affect what you've just described because if you already had lots of potassium outside...

compared to normal, then its gradient, in terms of its concentration gradient, not the electrical gradient, it's not, even though the door's cracked open, it's not wanting to come out as quickly as it normally would. Yep. Therefore, making the inside of the cell more positive, which then makes it, which you're going to get to, I guess, more likely to depolarize, right? Yes. So...

What happens is if you've developed this nice resting membrane potential of negative 70 millivolts inside the membrane compared to outside, it's at rest now, hence resting membrane, but it has the potential to change. Now, what we need to do to change it is to make the inside go from negative to positive. And the way that we do that is by throwing positive sodium in. Predominantly, that's the way that we do it. So...

The great thing is when you want to stimulate a neuron to send a signal, you open up sodium channels to throw sodium in. Now you can do that by, like you were saying, you can mechanically distort sodium channels through touch. So if you're a sensory receptor in my fingertips, if I press the table, the physical depression of my finger on the table actually pushes on the receptors and opens the channels for the sodium channels and the sodium can leak in.

And if you've got positive sodium leaking in, it goes from negative 70 to become a little bit more positive, maybe negative 65, then negative 60, then negative 55. And the thing is negative 55 for a neuron is what we call the threshold.

Once negative 55 is reached, that is the key to open up all the sodium channels. And if you open up all the sodium channels, you now get a huge rush of sodium into that neuron. And that is what sends the electrical signal down that axon, what we call the action potential. So that's really important. We've just now sent an action potential. Now to go back to your point about all that potassium outside, right?

If you had too much potassium outside of your cells... Which is called hyperkalemia. Hyperkalemia. When it comes to generating the resting membrane potential, it doesn't get to negative 70 because the potassium won't leak outside. So it stays closer to the threshold, which makes it easier for the neuron to fire off. Now, if it makes it easier for the neuron to fire off...

We're not talking about muscles here per se. We're talking about the central nervous system, like the brain itself. You could have seizures, for example. But of course, it also could be muscles. It could be muscles, yeah. So it could be hard. That's why you get dysrhythmias. Yeah. And also cramping or whatever in skeletal muscles. Yes. Yeah, exactly right. Or if you have so much potassium, it can depolarize and contract and then never reset. Right.

Right? So then it contracts once and then not again. So it could even stop muscles from contracting like the heart if you really have huge amounts of potassium. And that's actually, I think...

of lethal injection in some parts of America still. They give huge boluses of potassium. Yeah. Potassium chloride and then that leads to a cardiac arrest. Yeah, one big contraction and then never to reset again. All right. So we've now set that signal. We've sent an action potential. It's gone down the axon and it's now hit the axon terminals. Once it hits the end of the axon, let's say that this neuron...

is, no, I said I was going to talk to another neuron. Let's say this neuron is talking to a muscle because that's the context of what we're talking about today. So this neuron is innovating a muscle. Once this action potential reaches the end, so all it is is sodium channels opening up and all this sodium entering, entering like a domino effect all the way down the neuron, the axon. Hits the terminals. It then triggers calcium to enter the axon terminal and

Once calcium enters the axon terminal, it tells these vesicles, these bundles, these packages of calcium. Oh, sorry. Once the calcium enters, it tells these... Matt looked at me weird. Thank you. These vesicles or bundles of neurotransmitters, in this case acetylcholine, to be released. That acetylcholine will be released from the neuron. It will diffuse across what we call the synapse or the synaptic cleft and then bind to acetylcholine receptors

on the motor neuron, on the muscle itself, on the sarcolemma. Once the acetylcholine binds to its receptors on the muscle, it opens its sodium channels to let its sodium in. Because remember, muscle is excitable tissue, just like the neurons. So it needs to let sodium in so it can depolarize, send an action potential and not send a signal, but contract.

Does that make sense? Okay. So that's sending that signal. Now, let's just say we're telling this muscle to contract and you can go, okay, cool. We've just spoken about how the brain can tell muscles to contract and perform exercise. But that is not the whole story, obviously, because...

You can't just tell muscles, you can't just say, I want to do a squat, Matt. So I've now just sent a signal down my neurons, nerves, and this muscle is now contracted and I've performed a squat. We need to understand an important concept first called proprioception. And I want you to define to our dear listener what proprioception is.

Yeah, okay, so this is just another form of sensory experience of the – well, I guess in this case you'd say it's the inner world. Internal environment. Internal. Because the sensory neurons that we spoke about earlier when we did the organisation –

Some will pick up stimuli from the outside environment but some will also pick up internal environment. Now in the context of exercise and movement, we do the brain because it is a big player in the way it coordinates our movement. It needs to know what our body is actually doing at every millisecond of the day but also in that movement.

So it needs to receive information about what the joints are doing, but also what our muscles are doing. So the way I think about proprioception is it tells you where you are in your own space, which is a weird, when I say that to students, they're like, what the hell does that mean? So then I always do this, Matt, close your eyes for me. This is difficult in the podcast, but people can get the picture. So Matt's closing his eyes. He's got his arms by his side. Now with your eyes closed, I want you to touch your nose with your left hand.

Yeah, now touch your nose with your right hand. Okay, he did it. He's not drunk for the podcast. Congratulations. Now you might think, okay, what an easy, simple, strange test to perform. But if you really think about it, when you close your eyes, how do you know where your nose is? When you close your eyes, how do you know where your hands are?

And you can say, oh, because I can feel them. But you're not actually touching your hand with your other hand and you're not seeing where it is. How do you know where it is in your own space? And that's because of proprioception. So we've got these receptors that are located in muscles, joints, tendons, you know, connective tissue that tell you how bent, stretched, contracted muscles, joints, tendons are. Yeah.

Now, I want to ask you the question, why is it important to understand this in the context of exercise? Yeah, well, if you think about it, when you are coordinating movement like that, particularly when a squat is not, you wouldn't say it's highly complex in the execution of doing that movement. You say that, but I've seen you do a squat and it doesn't look like you know what's going on.

That was just me using the toilet in the bush. Sorry. You did a terrible job. So, yeah. So if you think about doing a squat maneuver in the gym, you're really just, you know, keeping your back straight and a lot of, you know, your knees bend in, you're keeping your kind of hip straight.

going into a flexion. So it's not highly complex. But when you start to do really complicated sports like, let's say, gymnastics or diving or swimming,

AFL in Australia where you are running, you're trying to coordinate where the ball or guess where the ball is going to go and try to catch it or jump for a big mark. Suddenly change position. Highly complicated. Or gymnastics where you're just doing flips in the air and so forth. Because that's all gymnastics is to me, just doing flips in the air.

So when you're performing that, your body, your brain, needs to know what every joint that's doing that movement is actually doing in real time. Yes. Without you having to look at it. Without you having to look at it. Yeah, exactly. Because you don't realize how – I mean if you think about right now if I wanted to pick up this drink bottle on the table, I can't propriocept –

to use that as a verb. I can't propriocept where the bottle is because it's not part of me. So I have to look to see where the bottle is in order to get it and pick it up. Yeah, that brings an interesting point because you and this, we can talk about it now. I mean, it will feed into a bit later when we talk about how to actually execute completely a motor movement. But let's use that example where you have a bottle on the table.

Now let's say it's not see-through, so you can't actually see the liquid, but you have an idea of how much is in there. Now you've already worked out from previous experience how much muscle, what's the word? Recruitment. Recruitment you need to pick up that bottle, but you've already kind of visually interpreted it.

So your visual system is in play here. But then when you go to pick it up, let's just say it's light as a feather. So I thought it was full. Really full? So I was projecting, I was thinking I know how much muscle I need to use to pick this up. But then I picked it up and in real time, what happens? Yeah, so let's just say it's not a bottle. It's just a big massive cup. What are those? You see everyone with these huge things, drink bottles now, right? Yeah. Anyway, let's say a big one of those where it's like a litre.

or a gallon in the States. Let's say six gallons. Four litres. Let's say it's a barrel. Anyway, so it's...

So it's big, right? So you think, oh my God, this is going to be so heavy. So I will recruit a lot of muscle, a lot of muscle fibers in my bicep. And now not with a T. Now when you go to do it, if you didn't have proprioceptors and it was empty, you would throw it all over your face. Yes. Okay. But the instant that you pick it up, you have this feedback straight away that says, okay,

This is how much tension my muscle is under and how much, you know, movement my joints is going through. You know what? I don't actually need much muscle at all. I'll just turn a whole lot off. And this is happening within milliseconds. And unconscious. And unconscious. So this is...

highlighting to some degree proprioception in the coordinating smooth, well-executed movement. But let's go back to what you were saying, which is a great example, but let's go back to your other example to further highlight proprioception with, let's say, playing football, right? So you're running, you've got to be aware of the other players, you've got to be aware of the ball, you've got to be aware of the umpire and everything else. So visually you're distracted with what's happening in the world. So you can't be focusing on...

your legs while you run and your arms and your body. And when you pivot where you move, how you move and how much you need to contract and, and, and push off and bend the knee and so forth. But your brain must continually get that information. And so that's coming from proprioceptors at all times, right? Yep. But it's also coming. So this is like multisensory modalities here. So yes, you've got all the proprioceptors, which is joint receptors, ligament receptors, joint capsule receptors, but also within the muscle, right?

which they sometimes call intrafusial, which is how much tension... Okay, so stop there for one sec because I want to ask you a question before you get to that. So you're running around on the football field and you're getting all this proprioception, which is great. You know how contracted and relaxed and bent and whatever everything is. But my question is,

That's fine. But what stops us from hyper extending at the knee or what's stopping me from extending my arm too far or contracting my arms too much? It's okay to know where you are in your own space. Okay. But what stops you from bringing those –

muscles, joints, ligaments into the extremes to the point of damage. So do proprioceptors stop us or help stop us or attenuate possible damage? Not just say, hey, this is where your position is so now the next movement needs to be this to get the football. Does it stop you from actually injuring yourself as well? Yeah. So the way it can do this is, again, we'll focus on the muscle proprioceptors now. So these would be

sensory fibers within the actual muscle belly itself and they are coordinating the tension on the muscle. Okay, so how taut the muscle is because when it's contracting...

and that's done by the actual contractile units of the muscle, it would be shortening. Now, if you don't have any sensory feedback to say the muscle's actually getting shorter, then the brain has no idea to know how much force to put into it because otherwise it will get all floppy, right? So what are these called? These will be interfusional muscle spindles. So these will be both...

very dynamic, so they're changing every millisecond, but they also demonstrate an overall static load. Okay, so that's important just to keep the muscle taut on both the agonist and antagonist side of the muscle. Because again, as we probably worked out, if you want to contract the bicep, right, you need to also relax the tricep.

To some degree, right? Yes. But if you relax the tricep and you have no sensory feedback that it's now all floppy or you need to keep it still a little bit taut because when you want to then do an extension, it needs to be taut enough to then take over as a contractile muscle agonist. Does that make sense? Yeah. So that's one side. Let me clarify because –

What muscle spindles do is they don't detect tension. They detect the degree of stretch. Stretch, I say, yeah. Right? So they're not measuring how tense the muscle is. The muscle spindles are measuring how stretched the muscle is. So let's... Yeah, the torsion, is it? Or just the... Just the length. It measures the muscle length and the degree of stretch because you've got other things that measure the tension. So let's just highlight here. So...

Let's say you've got a football player and they've got the muscle is stretching for some degree. Okay. Okay. Let's just say, let's take an example right now of I'm,

You've told me to hold some textbooks in front of me, right? So in the position of a bicep curl. So you put one textbook on my two hands and my biceps need to contract so that the muscles are shortening, but there's a degree of stretch on the biceps.

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I can't tell you how often I hear, "Oh, I'm a little OCD. I like things neat." That's not OCD. I'm Howie Mandel and I know this because I have OCD. Actual OCD causes relentless unwanted thoughts. What if I did something terrible and forgot? What if I'm a bad person? Why am I thinking this terrible thing? It makes you question absolutely everything and you'll do anything to feel better. OCD is debilitating, but it's also highly treatable with the right kind of therapy.

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If you think you might be struggling with OCD, visit nocd.com to schedule a free 15-minute call and learn more. That's nocd.com. Walk through what happens here if you were to continue putting textbooks on my hands, specifically focusing on muscle spindles. Of just the bicep. Yes. So as you keep loading the textbook up, the muscle will be stretching because you are forcing that.

the weight of the books is forcing the bicep away. Okay. So it's actually trying to lengthen the muscle. Now, the way that the muscle spindles are working, they are feeding back to the central nervous system saying we're getting stretched here. Therefore, we need to send more muscle

Different motor contractile effects here. This is the alpha motor neurons. So they're saying, hey, we need to recruit more muscle fibers in the bicep so we actually contract it more powerfully. And you can keep...

increasing, increasing, increasing, but it's going to get to the point where you won't be able to hold a whole library of textbooks, right? Otherwise, you're going to rip your muscle apart. So as the muscle lengthens because there's more weight on my hands, the muscle spindle stretches. That sends a signal into the spinal cord which sends a motor signal back out that says, I'm going to resist the stretch by contracting. That's right. Okay. I mean, mind you, this is an isometric, so it's a bit...

Sure. But it's still the same idea. So let's say now, like you said, you've nearly loaded the entire library onto my hands. There's obviously going to be a point where that muscle spindle is going to be stretched and goes, you know, it can't just keep saying contract, contract. That's right. The muscles have...

A limit. A limit. So how do I protect myself from not tearing my muscles off my bone or tearing my ligaments off my bone? Yeah, so here you've got – luckily you've got some receptors in your tendon muscle junction and they're called the Golgi tendon organs.

and they register the force that's getting put through the muscle. And so they would get to the point where they're registering this is now becoming noxious or damaging. So they'll start to become activated and when they activate, instead of...

being excitable to a muscle, they actually become inhibitory. So they go to the bicep and say, you've done enough, I'm turning you off. Ah, so it's protective in that sense. So muscle spindles are stretch detectors and Golgi tendon organs are tension detectors. And so that goes back to your sports analogy. If you are running or coordinating these movements and you, let's say, land awkwardly,

and you've put so much force through one joint, it may be so overloaded that they actually put an inhibitory response in and that kind of causes you just to fall over or something to protect the joint. Makes sense. Or the tendon or the muscle. And there's a couple of different –

in our joints. So we've got free nerve endings, which are the most abundant. So they're there for touch and pressure. You've got Golgi-type receptors. Now this is different to the Golgi tendon organs. And the Golgi-type receptors, they're found in ligaments around the joints and they tend to detect the joint angle and stress. And you've got Pacinian corpuscles. They're more so in the tissues around the joints.

And again, they detect joint rotation. So you've got multiple proprioceptors here to help detect the degree of tension, stretch, rotation, extension, and so forth as well. So there's a lot of proprioceptors. So it highlights how important proprioception actually is. Now, before we bring the whole picture together, let's talk about the motor neurons. So the neurons coming from the brain going to the muscles to innovate and talking about what we call motor units. So...

How many motor neurons are there in regards to the motor neuron pathway? Two, two. Okay. So if I were to go from your brain to your quadriceps, it only is two neuron pathway. Yeah. Okay. Not to say there's only two neurons. It's just a two neuron pathway, yeah. So...

Where does the first neuron start and finish and where does the second neuron start and finish? So if it's the quads, quadriceps, you would have a brain region in your primary motor cortex, which is precentral gyrus.

Which is what? Is that frontal lobe? Frontal lobe, yeah. So if you think about your right quadriceps is the one you want to move, it would be actually on your left hemisphere of your primordial cortex and there would be a region in that whole cortex that would map to your quads. Just talk a little bit more about that. What do you mean by that?

Well, there's a body representation in your motor cortex, which is called the homunculus. Yeah, homunculus. Little man. Little man. Which was my nickname in high school, the homunculus. Because it's got big lips, big tongue, massive hands. That's right. Small, small rest of the body. So your body is mapped neurologically, both in the sensory compartment, but also in the motor. Yeah. Now...

In that part of the cortex on the left side of your brain, there would be a region that would have the upper motor neurons for the thigh. For the right-hand side. For the right-hand side. So hypothetically speaking, if you were doing open brain surgery and you had a- Which I tend to do often, yes. And you had a stimulating electrode and you zapped-

through electrical impulse. Is that the technical term? That part of the cortex. It would cause the quadriceps to contract or move. So this can be mapped out and I'm guessing this is probably how it was done.

They probably worked out through strokes and those kinds of things when those areas are damaged, you become paralyzed in those regions. And strokes or brain injury would have measured that or demonstrated that. But then in situations where a person may have open brain surgery where they are awake still...

But the surgeon is able to electrically stimulate those regions of the brain. They can work out or map it, let's say. Yeah. Because remember, the brain doesn't have sensory receptors. So the brain actually doesn't experience pain. It just perceives it, right? Yes. So that would be where all the dendrites are for that cell body of the upper motor neurons for the quadriceps. So where does that finish?

Well, then they go through a really long axon.

They cross over to the other side of the brain, go down the brainstem, go down the spinal cord until it gets to the point where you want it to exit the spinal cord, which would be around, if it's a quadricep, I think L2, L4, lumbar 2, lumbar 4. So around about the level that it exits is where the upper motor neuron will finish and it will synapse with the lower motor neuron. That's right. In the ventral horn. So this is the front part of the spinal cord in the grey matter still.

And then you would have the lower motor neuron, which would speak to it in that synapse that you spoke about. And then that would exit. Now we're on the right side of the body. So where's the cell body for the lower motor neuron? In the ventral horn. In the ventral horn. Okay. And then it will exit out through the spinal nerve and travel down into the belly of the

and then innervate the nerve itself. Okay, so beautiful. Thank you. When we think about that lower motor neuron, so let's say you've got one lower motor neuron that's exiting. As it exits and becomes a peripheral neuron...

It will branch. It creates what we call collaterals. And it can branch, you know, dozens to hundreds of times. And each branch of this… Or thousands of times. Or thousands of times. Each branch of this low motor neuron will innovate a single muscle fiber. Which is a muscle cell. And that's an important distinction. That's the same thing. Synonymous, right? Synonymous.

So one lower motor neuron can innovate multiple muscle fibers, AKA muscle cells and tell them to contract. And this is important because this is what we call a motor unit. So a motor unit is effectively each motor neuron and all the muscle fibers that it innovates. And so interestingly, we can think about how we recruit muscles for contraction, because if I said to you right now, Matt, Matt, I want you to do a squat, right?

And you're just going to do a squat with no weights on your back. An air squat. Okay. You're going to be squatting the air, which for you is probably a difficult task, which is fine. Submaximal. Nothing wrong with that. I would say it's probably one RM, but let's say Matt's doing this task. As he goes down into the eccentric portion of the squat, obviously muscles are stretching, muscles are contract. And then he needs to go into the concentric portion where he's ascending up. He

Because there's not a great load on his back, he doesn't have to contract every muscle fiber of the prime movers here. He only needs to contract the minimal number of prime movers.

The question is which ones get told to contract first? Because if I continue to put a load on your back, you need to recruit more and more muscle fibers, which means you need to recruit more and more motor neurons. So how does the body decide which motor neurons to recruit? And this is what we call the size principle. So effectively...

The first motor unit for recruitment is that that's smallest in size. And generally the size of the motor unit correlates with the muscle fiber type. And we've spoken about muscle fiber types before, but let's just reiterate. You've got type one fibers, which are slow oxidative fibers. So they contract slowly. They use oxidative phosphorylation for their energy. So they're basic, they don't fatigue.

And we often use these muscles for endurance exercise, but also the muscles that allow for us to like our spinal erector muscles, the muscles that... Core, posture muscles. Yes, they're these type one fibers as well because we don't want them to fatigue. So they're the first to get recruited because they tend to be the smallest in size.

Then, and it also makes sense because if I said to you right now, do as many air squats as you possibly could and compared it to how many squats you could do with 100 kilograms on your back, you'd do far more from the air squats. Even though you're recruiting fewer fibers, they don't get fatigued as fast, right? So that makes sense, doesn't it? Yeah, in a way it'd probably be, particularly if you've got

...an idea or memory of this movement already. And you think, oh, air squat's pretty easy. It's not a difficult task. Parts of your brain that...

what would you call it, draft out what the movement's likely to be. It probably is similar to just walking, right? It's like I don't need much more muscle than I would to walk. Yeah. And so as the weight gets added to your back, you're going to start recruiting larger fibers, larger motor units. And so the next type is type 2A. So these are fast. They're fatigue resistant to a degree. So it's sort of like a mixed fiber type between –

using glucose, so glycolytic and oxidative, but they're a little bit bigger. They're an intermediate size motor unit. And then I really need you to contract. You need to recruit a lot of muscle to produce a lot of force. Then you're going to have to recruit the type 2X fibers. These are the fast glycolytic. They fatigue very easily, but they produce huge amounts of force. And the reason why is because they're big or large motor units. So that means –

The motor neurons innervate huge amounts of fibers. And that makes a lot of sense, right? You start to recruit less and then you recruit more and more and more. So with this said, with the context of exercise and doing things in the gym and so forth, when we look at strength gains, particularly when we start a new regime, is a lot of the strength that we develop early on

to do with just better motor recruitment? Yes. Yeah, it is. And it's still a relatively contentious topic of conversation or even for debate. But generally speaking for untrained individuals, a lot of the early gains are neurological. In strength, that is. In strength and neurological. Just you have a better, more efficient way of activating those bigger muscle fibres. Yeah, you've got better control of your motor unit recruitment.

But then as the time progresses and obviously you'll hit a degree of plateau on the neurological end, then you start getting hypertrophic gains and you can get muscle size gains. You can become more efficient in the energy that you use. Some fiber types can become a bit transitional sometimes.

Right? Depending on the types of exercise that you try. So there's a whole bunch of things. You can also become more efficient in the way that you utilize your neurotransmitters. So recycle them and release them. You can be more efficient in the way that you... Even the movement, right? Just a more efficient movement. Yeah. Which is then required less maybe stabilizing. Do you know what I mean? Like if you actually have a better...

I'm guessing, and you're not like clumsy when you do the movement. You become more efficient. Yeah. Yeah, absolutely. You know, you're better at clearing away the metabolites that you build up. You probably produce less metabolites because your body has adapted. So it's become more efficient at using the energy and producing the metabolism. So it's a whole range of things that happen in regards to what produces the fatigue during exercise but also what can mitigate that fatigue. Okay.

So let's talk about now how we actually move, how we actually perform motor activity. So exercise. And I think we might as well just stay in the squat context. Sure. Because, again, it's fairly simple in understanding what it looks like. So the way I like to think about it, and correct me or stop me, I know that you like different analogies to me, so that's totally fine. What?

There's a whole bunch of discrete areas of the brain that need to be activated in order for you to perform what seems to be a simple movement like a squat. Crazy complex, even though it's a simple squat. Yeah.

So we used to think that the motor signal initiated at the motor cortex, like you said, prefrontal gyrus, little strip of the cortex, couple of millimeters thick. It's got an area of, let's say, all the muscles required for the squat located there. And it says, well, I need to squat. I'm going to initiate the signal here.

The evidence is saying that while yes, this is involved, there's other subcortical and cortical regions that also say, I want to squat. And I like to think about this and you actually gave me the thought of using this. So it's effectively your analogy. The president, I'm not saying the current president, I'm just saying a president, right? Would say, I want to squat. That's just, that's it. I want to squat. Right.

They've got no plan. They've got no idea how they're going to do it, but they know they want to squat. This is coming from the subcortical and cortical regions. It then needs to send that signal to accessory areas, association areas. And it's the association areas which are like the little minions, what would you call the... Like the ministers or the advisors? The two ICs, the advisors that surround the president. The president says, I want to squat. Okay.

And then walks away. And the advisors who are the association areas, they create a draft plan. Okay. In order to squat, we know that we need these five muscle groups. I'm just throwing a number out, right? And we need those five muscles to contract in some particular order. So to be anatomically accurate here, are we talking about the premotor and the supplementary motor areas here? Yes. Okay. Yep. So premotor being the motor cortex and then the supplementary and association areas. Yes. Okay. Okay.

So it says, okay, I've got a plan. I know what I want to do. I want to contract these muscles in this order. That's what the association areas allow for us to do. But it needs to ask for permission. So it needs to go to what, the Senate or the... Yeah, the Congress, yeah. Congress to ask for permission. This is the plan. This is what we want to do, right? Now, most presidencies will go to Congress and ask for permission. And that's what this one's doing as well. This is what the brain's doing. So...

in this instance, is going to be the subcortical region. So this is the basal nuclei and the cerebellum. So what the basal nuclei does is it will ask the basal nuclei for permission. It says, I want to squat. Can I squat? And the basal nuclei will say, yes, you can squat. So it gives it permission to initiate the movement. Okay. So hand break off. Hand break off. Yes, exactly. And we'll go back to the basal nuclei after we go through all this if you want.

It'll also talk to the cerebellum and the cerebellum and I think what you said about this is really nice. The cerebellum is like, well, before we put this plan into action, right, we need to ask people who are actually on the ground whether this will work, right? We need to ask the real people that deal with this day-to-day, is this going to work?

And if they say yes, then we'll put the, then that's the cerebellum. So the cerebellum is constantly working with proprioceptors, right? Which is saying, yeah, tweak that, move this. That's too extended. That's not. So that's getting the real feedback from the ground. Then once you've got the thumbs up from both the cerebellum and the basal nuclei, it goes to the thalamus, which is basically the sorting center. So this is the post office. It's printing what needs, it's printing the plan that needs to be sent out.

...and that plan that needs to be sent out then goes back to the cortex...

And the cortex says, all right, I'm going to fire off these upper motor neurons, which then fire off the lower motor neurons, which then innovate the muscle itself. And that's how we get motor movement. Does that make sense? It is. So then once the contractions are taking place and the person is starting to initiate the movement, as we spoke about a little while ago, the muscle, the joints are now moving. So you...

within the higher brain centers had an idea of what that squat should look like. But as you are in motion, then you're constantly getting feedback from the body. And this can be from the eyes. Well, let's say you're squatting with your eyes closed. Okay. What feedback are you getting?

Well, you're going to have all the proprioceptives, proprioceptors, and that's not just of the muscles moving the leg, but it's also the proprioceptives of the core. They need to be contracted to give you a solid base to work off, right? So you're getting all the muscles that need to be activated to coordinate that movement, but you also got the vestibular apparatus or the center, right?

which is your middle ear, which gives your body or your brain an idea of what your body's actually doing as well in space. Is it moving forward and back? Right. Or is there angular rotation or are we static? Any degree of acceleration. Is our head moving or are we static? So this is not going to be as important, let's say, in a squat as it would be if you're running in AFL and you're trying to work out what angle I need to run. Now I've got to jump. I'm in the air.

...where I put my hands and so forth to take the mark. So that's a bit different but... So if you open your eyes now, in what way are the eyes contributing? Well again they're giving information about the environment...

they will tell your brain what your body's actually doing as well. So you've got vestibular, you've got eyes, you've even got hearing, and that's going to go into the brainstem, which feeds into the vestibular nuclei, which is in your brainstem, and then that coordinates back into your cerebellum. So your cerebellum is getting all this information, sensory information,

All the time. So while you're doing this, it's getting – and these, particularly the proprioceptive pathways, they are some of the biggest, largest and most myelinated pathways.

nerve fibers in the body. So they are large, you know, the bigger, the axons themselves are bigger than 20 microns in size with a lot of myelin. So they are, the electrical speeds are over a hundred meters a second. Yeah. And it makes sense because you need, your cerebellum needs to be receiving real time signals from

Every millisecond as you're moving. Yes. Otherwise you'll overextend or you'll contract too much or whatever it might be. And so just to think about that, what your cerebellum needs to be doing to refine, because it is getting the pattern from those –

and the supplementary motor of what a squat should look like. And then it's getting feedback on what you're actually doing. And if it's not matching up, the cerebellum needs to manipulate, iron out the movements with the basal ganglion all the time, just to make sure this movement is concise. Yes. Not concise, but just smooth. Yeah. And matches. So phenomenal how this happens so beautifully. Yeah. And we don't fall over more often. Uh,

And then if you think about it, if you start to have cerebellar effects, most notable example if you're drunk because alcohol inebriates the cerebellum. So its ability to coordinate posture, muscle tone, movement, balance is inhibited. Balance, coordination and muscle tone are the three major things that the cerebellum controls. So if you are drunk, what are the effects? Well, you're not going to be able to maintain posture. So you're...

A bit wobbly. Wobbly. Yeah. But you're not also going to coordinate those movements well. So it's going to be all over the shop. Hence the close the eyes and nose touch in the U.S.?

Or just walking heel to toe on the line. Yeah, walking the straight line. Because again, you can't coordinate looking at the line whilst proprioceptively executing that. Yeah. And you can do clinical tests for this and this would be ataxia or tremors, particularly the difference between a resting tremor versus a movement tremor. And that's all telling that you may have impacts either with the basal ganglion or the cerebellum. So you can have something called cerebellar ataxia. Yeah.

A stroke could lead to a stroke in the cerebellum. And there's cases of cerebellar. So you can have congenital cases, genetic cause cases. And I think there's a family in India who have a type of congenital cerebellar ataxia where they walk on all fours because standing is not something that they can do, at least not easily. But also if you have a cerebellar ataxia, what can happen is if you close your eyes, you fall over. So what this highlights is that your eyes are very good at overriding the

your cues, your sensory cues, even including proprioception, right? So there's an experiment I do with my students where I get them to wear the drunk goggles. So the drunk goggles just distort the way that you view the world and I get them to walk the line heel to toe and

Even though their proprioceptors are great, they're not drunk or anything like that. The vestibular is fine. They can't do it because the visual system tends to override. So it's telling us how important and strong the visual system is for us for motor movement. Yeah, you said that in…

associated with, you know, boats and motion sickness. I get terribly, terribly sick. I'm mismatched. So the visual proprioception, the stibula are mismatched and wherever the brain is mismatched, it just makes you feel sick. That's right. Because it thinks that there's, you've got a toxin in your body and you need to vomit it up. Now the basal nuclei. So we spoke about the cerebellum important for balance, posture, coordination and muscle tone. But,

But we said that the basal nuclei is important for initiating movement, and that's true. But effectively what the basal nuclei does is that the deep subcortical areas that have multiple nuclei associated with it, and effectively it will receive that signal saying, can I move? Now what the basal nuclei does is it evaluates that signal and

And there's two simultaneous pathways that are present within the basal nuclear. One that says, yes, you may move. And the other one that says, no, you can't move. And that's important for regulating motor movement because sometimes you shouldn't be moving, particularly if that movement is going to contravene something that you're already performing. So it might cause injury or you're contracting the antagonistic muscle. Right now you don't want to contract two antagonistic muscles, things like that, right? Mm-hmm.

So you've got two signals, but both have been stimulated. Both are saying, yes, you can move. The other one's saying, no, you can't move. And this is where dopamine comes into play because we've got these neurons. We've got a collection of neurons in an area called the substantia nigra.

and specifically substantia nigra pars compacta. And it's an area that have neurons that produce dopamine. And these neurons extend to the basal nuclei or nuclei within the basal nuclei.

and release the dopamine. And effectively what dopamine does is it stimulates the yes, you can move pathway and inhibits the no, you can't move pathway. So if you stimulate the yes, you can move, it promotes movement. And if you inhibit the no, you can't move, it promotes movement, right? Because you're stopping the stop signal.

That's one of the reasons why dopamine is so important because it allows for us to initiate that movement. But because like you said earlier, the basal nuclei is always evaluating that signal, it helps smooth the movement out. Now, that's important because in order to smooth the movement out, you need to be able to fine-tune the stop-start signal, right?

For some people, they've got Parkinson's disease, which means that substantia nigra, the dopamine-producing neurons, they're dying off for whatever reason. We don't actually know why. We've got a lot of theories behind it.

but it means that those neurons aren't producing dopamine and the dopamine's not working at the basal nuclei. So that means you are constantly receiving a stop-start signal. So people with Parkinson's disease, it's very difficult for them to initiate a movement because there's that stop-start, stop-start, but also they can't smooth the movement out very well. So they have a constant stop-start signal at rest, which is the resting tremor. Now, I think it's important to say that people with Parkinson's disease, while they find...

initiating walking difficult and changing direction or speed difficult once they've started walking and a better example is riding a bike it's very easy to just continue doing that movement

And one of the theories here is that the spinal cord has pattern recognition or pattern generating… Yeah, central pattern generators. That's right. That allow… that basically take over and say, don't worry, we're going to just take over from here so the higher regions, the higher order regions of the brain don't have to deal with it and we'll just deal with these constant patterns that are repeating over and over again like riding a bike. Okay.

This is one of the reasons. Or walking. One of the reasons why people with Parkinson's disease can very easily ride a bike once they've started. Which is cool, right? Very interesting. And that feeds into a little bit what our research group has looked at where in the spinal cord injury,

The last two clinical trials that we've done have been looking at high-intensity exercise rehab and finding that individuals with spinal cord injury, whether it's a high injury or a lower injury, that they are getting quite significant results

both in general health but also in motor movement and so forth. And it's probably because even though the rehab hasn't helped improve the lesion at the spinal cord, it's probably incorporating or activating more of these

spinal cord units, central units to then improve movement and those kind of outcomes than they thought they would have ever had. You know, a lot of the time...

when individuals have their spinal cord injuries and then they do their acute rehab within the hospital setting and they have certain improvements, probably to a degree impacted by the swelling has gone down, the inflammation has gone down, so there might be slight improvements. But after a certain number of weeks, many of them are told this is the best you'll get for the rest of your life. But no further do they do high levels of rehabilitation

exercise or those kind of movements anymore because they're told it's not going to be beneficial you won't be able to contract your legs in that way anymore yeah but when as we saw in our clinical trials they go to very injury specific centers ours was in burley heads in queensland and they was a whole gym set out with exercise physiologists that were

for spinal cord injury and they had all their equipment which was specific for spinal cord injury. And all the participants, you and I interviewed them to see the difference between what they were like at the start, 14 weeks later doing five days a week was profound, right? Their mental health, their physical health, but also what they could perform from a motor standpoint was remarkable.

just by the potential of doing these kind of spinal cord, um,

Feedback loops, I guess you'd say. Yeah. That's a great segue into the neurological benefits for exercise, which I think is the part that we're up to now. How can exercise improve our brain health? Or nervous system. Or nervous system, yeah. I mean brain health is sort of like the way people broadly, colloquially refer to it. But yes, how does exercise improve the nervous system? This is something I find interesting because –

And I'd like to get your opinion on this. You've heard the term panacea before, right? Something that supposedly is a cure-all. Now, there's no such thing as a panacea. There's nothing that cures everything. And if somebody states that there is something that cures everything, then it's not going to be true, right? They're probably making money off it. They're probably making money off it, exactly. But I tell you what, I would say that exercise is the closest thing we have to a panacea.

Because, you know, usually when you and I do our research for these episodes and we look at, you know, the way a drug… The current evidence. Current evidence and the way a drug works, you can say, okay, this drug might do half a dozen things because it will specifically bind to this receptor and here are the downstream mechanistic effects and this is what happens. When you look at the research for exercise on nervous system benefits and

This is a bit of hyperbole, but effectively you could take any objective marker and it improves. So you could say, what about cognitive function? Yeah, it improves from exercise. What about memory and learning? Yeah, it improves from exercise. What about the rate of depression? Yeah, it diminishes. What about blood flow in the brain? Yeah, it improves. What about neuroplasticity? Yeah, it improves.

I can't tell you how often I hear, oh, I'm a little OCD. I like things neat. That's not OCD. I'm Howie Mandel and I know this because I have OCD. Actual OCD causes relentless unwanted thoughts. What if I did something terrible and forgot? What if I'm a bad person? Why am I thinking this terrible thing? It makes you question absolutely everything and you'll do anything.

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So, you know, effectively exercise, you could broadly say, globally improves the nervous system and nervous system function. And I don't think that that is much of an exaggeration. And I think that's why pharmaceutical companies are looking at how can we bottle exercise up into a drug? Well, okay. And that's a great point, right? Because...

That would be a common thought process. You go, well, we know exercise is so good for so many things, including benefiting the nervous system and the brain. So how can we figure out how we can bottle it up and give it as just like a pharmacological intervention? But here's one of the differences, and this is where I want to get your thoughts.

When you take a drug, the drug has a drug target, which tends to be, let's say, a receptor. And once it binds to the receptor, it has a range of downstream effects that you can follow and you follow those mechanistic effects to a particular outcome. When you look at exercise, because it's a systemic thing, when you exercise, you move all these muscles. So I can't think of an organ system of the body that...

altered through exercise, right? And anytime you tell an organ system to do something, it's going to release products.

So you're going to have your whole environmental milieu of the body will change due to exercise, right? And so I'm a researcher. I want to look at the effects that exercise has on the brain and I go, oh, wow, I see that this one marker, let's say BDNF, a neurotrophic factor, it goes through the roof when people exercise. And at the same time, their memory gets better. So BDNF...

...must be what causes improved memory from exercise. Let's bottle up BDNF and give it as an injection for people to improve their memory. This is the flaw in the thinking that it makes general sense to think about it like that. But there's a lot of steps in between because when you exercise... ...the whole systemic effects, the changes that is elicited in your body...

results in thousands, tens of thousands, hundreds of thousands of chemicals being released that interact, that change and affect multiple things. So to say, oh, it's BDNF doing this is absolutely

An oversimplification and even the researchers would agree that that is an oversimplification. Hence why BDNF right now isn't marketed as something for people to take to improve their health, right? Do you agree with that? I think you've summed it up well. It would be similar to if you looked at what are the chemical changes within the body during an infection and looking at the chemicals that the immune system uses

are using to communicate amongst each other. And then trying to say, well, here we need interleukins, here we need tumor necrosis factors, here we need cytokines. And then doing the same thing as, okay, if you want to do better when you have an infection, just inject yourself with a whole lot of these cytokines and you'll be good. Yes. Like it's so complex to think we can simplify it in that manner. Yeah. It's probably a bit of hubris. And, you know...

The thing is that, you know, you say, oh, let's bottle exercise. Why bottle it when we can just perform it? I mean, and that could be an ableist thing for me to say as somebody who at the moment can perform exercise with very little trouble or issue. Yes, I get that, that I can go and go for a run if I want or I can do weight resistance training or whatever and some people are probably limited to be able to do that. But I would say that, you know,

Most if not all people can do some degree of exercise and improve upon their current health and wellbeing through exercise in some regard, right? And this is where the research is really interesting. And you brought this up to me earlier about the fact that

There's so many different types of exercise. So do the benefits lie in certain types of exercise or is it just in exercise? Yeah, or the duration, the intensity, the type. It's very difficult. The answer is yes. The answer is all of it, right? I mean...

The way I see it, and now Matt and I are delving into the area of personal opinion here, so we'll just delineate the part of the podcast where I want to give you my opinion, which is based on the evidence that I'm aware of, but I could be totally wrong. The way I see it is that if you haven't done exercise or you don't regularly do exercise, doing any form of exercise will benefit you and your health, including your neural health.

If you are somebody that exercises every day, then you might find that doing specific types of exercise, so certain modalities and intensities, might benefit you in other ways, right? More specific ways. But maybe not. Maybe the benefits of exercise are simply from performing the exercise because it is that adaptation to stress, right? And so, again, take somebody who's never done exercise, right?

And you say, I'm going to, so let's take two people who've never exercised. This is my thought experiment. I know that this is scientifically flawed, but this is my thought experiment. I'm going to take the first person and I'm going to get them to do gradual exercise that builds over time. I'm going to get the other person and from day one, they're going to do the hardest intensity exercise I've ever done.

I think what I'm going to find is the person who gets the most benefit will be the one that gradually increases over time because probably the very first workout I give the other person of the high intensity that goes beyond what they should be doing is harming them because the stress that they're exposed to has gone beyond what their body can recuperate from and adapt to. Does that make sense? Yeah, it does. So for me...

Exercise is, from my perspective, as long as you are performing some degree of cardiorespiratory and resistance training that continually exposes your body to a degree of stress that is sufficient for adaptation but not beyond the body's ability to adapt to,

I think you're going to get health benefits. Yeah, and that speaks to the concept that we spoke about a few episodes on hormesis, right? Yes, yes, yes. Was it the U-curve or the tick curve where doing nothing, it's going to –

have a detrimental effect but starting to do some things, whatever that is, has a benefit. Now how wide that is we don't really know because it's personalised but then if you go too excessive it's now going to become detrimental again. Yes. And that's the balance that we need to look for ourselves and fit in. And like you said, exercise is the thing we're trying to promote here and for a person to perform it you need to have balance

motivation and want to do it. And so therefore you need to find things that you enjoy doing. And that's sometimes where I find I get a little bit frustrated with some of the health influences that try to prescriptively tell you what you need to be doing specifically. Yeah. And they bring angst and anxiety into the individual to think, oh, I should be, oh, I must be doing this.

I don't know, 25 minutes of a HIIT workout twice a week. Otherwise I'm not going to get these BDNF levels or whatever, right? Yes. But in fact the most important thing here, it's a bit like diet, the most important thing here is to actually just be doing stuff. Yeah, consistently. And finding what you enjoy doing because that's more likely to allow you to continue it

But also then once you kind of get to a point where you're doing it more regularly, it becomes habitual. And then you probably will find you start to do more things that you once may not have wanted to do because you start to have those systemic changes where you are feeling better, more energy and wanting to explore different things. And don't be distracted.

From the wellness influencers who say things like highlighting one particular chemical being upregulated at a particular time. Because you had a great analogy that you said to me. Can you tell the analogy before that you said to me earlier? Well, this is a bit like what we've heard with Alzheimer's disease being a form of dementia. When we look at brains of individuals who have Alzheimer's

had this condition and they've had autopsies done and they have a look at what's actually structurally changed in the brain, they've found that in certain regions of the brain we see certain plaques, tangles that are... What are plaques and tangles? Just, you know, are proteins the way that proteins are folded or aggregated?

You know, you can think of a neuron. Neurons have, like we described, it has their dendrites, it has their cell bodies, but also has long axons. Now, in the axons, they need to be sending communications between, because as I said, some are a metre long. So what goes down at one end has to be communicated back up to the body and likewise has to be sent back down to the axon.

axon terminal. And the way that they communicate or send things, they need to have protein channels, protein tubes, cytoskeletal structures to give strength to the neuron. They're proteins. Now, if they start to misfold or aggregate or clump, that can cause disruption to the cell activity.

And certain brain pathologies, dementia is a good example, but also the condition, what's it called now, CTE, chronic traumatic encephalopathy, where you have chronic...

Traumatic injury to the brain through concussions and so forth or sub-concussions over long periods of time. In certain sports like football, you know, the good movie documentary about that with Will Smith, I think. But that indicates that certain brain regions develop these pathological changes. Now, for many decades, I guess, scientists thought that Alzheimer's was caused by tau protein deficiency.

These plaque accumulations. Plaques or neurofibrillator tangles and so forth, which is…

It makes sense. It makes sense because there's an effect there. Healthy people don't have it. People with the disease do have it. Therefore, these plaques and tangles must be the cause of dementia. That's right. The analogy that I gave was like let's just say in your neighborhood you all of a sudden had a youth crime problem and one of the things that the youth were doing was graffitiing everywhere.

that would be a change in the neighbourhood. Now, if you just went around and removed the graffiti, you're not solving the issue. There's still the fundamental problem of the youth crime causing changes in the neighbourhood. Similarly, if you only target the protein tangles and the...

you're not necessarily getting to the root cause of what it is. You're more looking at an association factor. Yeah. And so this speaks to, I'm not sure what you're going with. Well, I was saying that don't,

When you hear wellness influencers focus on one chemical, IGF-1, BDNF, this is what's causing all the changes, the neuroplastic changes, this, these benefits, that benefits. It's a misdirect. Yeah, that brings a good point. So when we look at certain neurodegenerative disorders, whether it is dementia, Alzheimer's, Parkinson's disease,

multiple sclerosis, even post-stroke. These are pathological changes to the brain. Now, exercise...

You can do these experiments or scientists have done these experiments where they have, let's say, rats or mice that have a predisposition to Alzheimer's, right? So they will develop these changes in their brain. Now, if they were to initiate exercise regimes to these animals, they have demonstrated that there's less dementia symptoms, less of these pathological changes in the brain.

What's the reason? Is it because there's a signaling protein that changes or are there other downstream effects like are we decreasing the amount of inflammation in the brain or are we changing the oxidative stress? All these other very nebular factors.

difficult to pinpoint alterations that you can't really specify necessarily easily. You can say that causally there's something around exercise that is improving, but to know exactly the mechanism behind it, we can only really speculate. Yeah, that's right. And I don't even think we would be able to hit that point where we could –

dial it down to two or three things. I don't think that's possible because it's systemic-wide. It's exercise. It's changing your body. You're stressing your body out. A whole bunch of things are happening. And it's very rare for me to go, I'm not saying I don't care about the mechanisms here because I do. I love all this sort of stuff. But when you jump into literature and you go, oh, yeah, exercise is good for nearly everything associated with

nervous system health, you sort of go, well, what's the point of going into the mechanisms when I know that the exercise itself is of benefit? I wonder if it's a bit like, and you sit in this research more where pain research, right? Where

a lot of things can benefit an individual with chronic pain. And, you know, just one that comes to mind is, you know, acupuncture. Yeah. Like anecdotally or even at a huge population level, there are benefits being demonstrated with acupuncture or even TENS machines, like those electric, what's it stand for? Trans something, neurostimulation. Yeah.

We don't know precisely or what it's actually doing to change mechanistically the pain experience for the individual. But for some individuals, it just works. So maybe it's just something that we accept as, well, there's benefit here. If it works for you, continue it. Similarly with exercise...

It's hard to pinpoint exactly from a mechanistic standpoint how it is actually doing what it's doing, but we know that there's profound benefit. I think there's a bit of a difference there in the sense that pain by definition is subjective. So if you're...

changing somebody's subjective experience of pain, then by definition, you've effectively altered their pain experience. That's true. But when it comes to the objective benefits of exercise, they can be measured. If we're not talking about the psychological benefits of exercise, which we haven't really touched upon here because- That's profound as well. It is profound, but that goes beyond our-

I can't talk about psychology and mental health. That goes beyond my ability. But there are significant benefits to that. But our...

Outside of that, when we look at objective benefits, we can. I mean, I'm sure that if I jumped as deep as I possibly could into the literature, I could get a collection of over a thousand molecules that are altered during exercise that are correlated with some degree of benefit. So does that now mean that's the milieu, the environmental milieu that I need to be in to get the benefits? Or is that simply just what we see when it happens and they're

You know, they're there because they are causative or they're just there coming along for the ride or they're just one small part of the cascade. I think the point we're trying to get across, even though we said the same thing over and over again, is that, you know, we could talk about exokines and myokines and metabolites and the microbiome and all the blood, the vascular changes and glymphatics. And I'm sure a lot of people would like to hear about it. But

Pick a structure of the nervous system and it's changed due to exercise in some regard and it's infinitely detailed and long and what's the use of it if exercise is the thing that changes those things for the benefit? I don't know. Maybe I'm oversimplifying it or even making it more difficult than it is. But I think my take-home point is that exercise...

as an intervention in some regard is beneficial to the body. Yes. And we should all be doing it. And more and more it's been recognised for that. Yeah. And more and more it's been recognised as part of your holistic regime that you should be doing

...want to say every day. Yeah. Like eating every day. You eat every day. Yeah. So exercise or move. Yeah. To some degree. And move in a way that you find enjoyable. Because even just doing those things that you enjoy... ...psychologically has benefit. But also just being out...

being exposed to... I mean, I was at the optometrist the other day to get my daily annual eye examination. Daily annual? Sorry, annual eye examination. You do have thick glasses. I wouldn't be surprised if you went every day. And the optometrist said... We're talking about... I forget how we got into the topic. Oh, I think I was just talking about noticeable age changes to my vision. Like certain things that I'm finding more challenging now is...

changing the light environment so if i'm going from inside to outside and trying to focus on things with contrast it becomes more challenging yeah and going from close up to long it just takes a little bit of time to catch up yes now she said that um in terms of artificial lighting versus

natural lighting is profound in our health and more and more like, I think she said something like that's that 2050 or 2040 in Australia. This is just Australia. Yeah.

Myopia? Most children will be short-sighted. Yeah. So myopic. Yeah. And I asked her, is that part of the reason for why, say, in some Asian countries, why almost every single person has glasses? And, yeah, she said because a lot of the time they not only are reading screens or reading things close up,

but also not ever being exposed to the outside natural lighting. It's a big part of reducing myopia is simply natural light, going out and getting natural light. And that's not necessarily saying direct sunlight. That's just all the ambient light that's coming from the sun, right? Yeah. So infrared versus ultraviolet being different wavelengths, but...

Because as we know, UV is going to have probably a detrimental effect on your eyes as well. So hence why we're instructed to wear sunglasses. Yes. Because it can change certain tissue properties in the eye as well as it does to the skin. But I guess my point there was with exercise, if you can maybe –

coordinate that with being outside, that's also having profound health benefits as well. Absolutely. I went to CrossFit with my wife yesterday. So my wife is part of it. CrossFit, she's done CrossFit for, God, over a decade now. She's very good, very fit. I used to do it early on.

Body's not super stoked on it right now, but I do it maybe once a week. So I go to her gym and we do a partner workout. So I work out with her. It was awesome. I mean, part of the workout was to do a run outside, right? Holding a medicine ball, going for a run, bring it back, and then doing a whole bunch of stuff inside. And just being able to get outside and exercise, I felt great for the rest of the day, right? Just great. And so there's so many –

physiological, physiological benefits to exercise that you can't discount. I mean, particularly for mental health. Massively. I heard something the other day on the health report and a professor of mental health, I think it was in Victoria, was just talking about...

Now, I've got to be careful here, but the way she described it, she would compare it to conventional treatments. Exercise. Yeah, exercise. Conventional pharmacological. That's right. And I don't want to go into that weeds because I don't want to sound like prescriptive, but just when they do clinical trials of comparing it to the gold standard, how exercise has, and this could be in depression or

anxiety disorders, how exercise has such a profound impact on brain health. Yes. And I think the important point here is that, yes, while exercise can have a significant benefit, you know, and in some instances very similar to that of the pharmacological interventions,

That is not to say that the exercise should replace the pharmacological interventions, right? So I think that's where a lot of people get confused. They go, oh, I may not need the drug if I just do exercise. But it's, well, I mean...

They don't have to be mutually exclusive, right? As you know we do with our physical health. You may, like myself, have a predisposition for plaque formation in blood vessels. So I'm taking pharmacologically statin, but that doesn't mean now – But you're also a vegetarian. Right, or it doesn't mean, okay, well now my cholesterol is taken care of, I don't have to worry about exercises. Like they still should happen concurrently.

Yes. Yeah. You want to put yourself in the best place possible. All right. We've spoken enough about this.

Thank you, Maddy. Thank you, dear listener. We hope that you're enjoying this series. Do you know what the next episode will be off the top of your head? I'm trying to think. So this is nervous system. Will it be cardiovascular or is it going to be muscular? Cardiovascular comes up, I think, muscular maybe. We're going to do muscular system as well. So we've done immuno. We've done nervous. We're going to do the muscular. So this is going to be a big one. Muscular system and exercise. Obviously, exercise.

Can't do it without the muscles. Matthew, thank you. Dear listener, cheers. We'll speak to you soon.

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