That Neuroscience Guy - How Your Brain Reacts to Being Sick

Episode Date: January 13, 2022

We've all been sick before, and that usually leads to a foggy, emotional, and fatigued state of mind. In today's episode of That Neuroscience Guy, we discuss why and how being sick changes your brain. 

Hi, my name is Olof Kregolsen, and I'm a neuroscientist at the University of Victoria. And in my spare time, I'm that neuroscience guy. Welcome to the podcast. We've all been sick. And I'm not talking about COVID necessarily, although the same arguments would hold true. I'm talking about the common cold or the flu. We've all experienced it, a running nose or a cough. But the worst part is the brain fog, being short-tempered or hyper-emotional, the apathy, the malaise, and of course the fatigue. That feeling where you just don't want to get off the couch. I have to admit, I have a cold right now, so this topic is of personal interest to me. So I dove into the research to see what I could learn, and I found it fascinating,

and I want to share it with you. So on today's podcast, the neuroscience of being sick. Well, at least while we feel horrible when we are sick. Somewhat surprisingly, emerging research suggests that the feelings of sickness that we exhibit and experience are actually beneficial to us. They enable us to divert our energy to fighting the viruses and bacteria that have entered our bodies. In other words, we feel sick because we are putting all of our effort into a war with what's making us feel sick, and there's just not enough left over to feel awesome. To understand this, we have to cover a bit of background, and specifically something called the blood-brain barrier. and specifically something called the blood-brain barrier.

Basically, the blood-brain barrier is a division between the blood that circulates around the outside of the brain and the extracellular fluid that surrounds neurons, and of course the neurons themselves. So in other words, the blood-brain barrier prevents blood from going into the brain itself. This is a bad thing. If you recall a previous episode, that's essentially what a stroke is. Now, for a long time, it was held to be true that the blood-brain barrier was impenetrable. Nothing could pass through it. Then over time, it was realized that it was actually selectively permeable. It would keep most things out, but it would let a few select things through. So scientists for a long time assumed that the blood-brain barrier would block signals from the human immune system, but it turns out that's not entirely true.

As proof of this, researchers from the University of Freiburg in Germany exposed mice to a virus that called them to be ill for a brief period of time. Then what they did is they tested the rodents for depression. Now the way this works is the mice were placed in a container of water, and what they have to do is swim around and try to find a way out. It's a little bit tricky. It's called a Morris water maze, and effectively there's a platform under the water at a location and the mice swim around until they can find the platform and stand on it so they can stop swimming. So there is a way out.

No mice drowned in this study. Now what happens with depressed mice is if you put them in the same container of water, they quickly give up and they just float. They basically go on their backs and they sit there and they float. And the assumption has always been it's because they're depressed. You might note similar behavior yourself when you're feeling down. I know that when I'm feeling a little bit sad and lonely, my ability to finish tasks is impaired and I kind of want to float on my back and give up as well. Now, what was interesting is that recall that some of these mice were sick. And the researchers found that the sick mice gave up even more quickly and floated longer than the depressed mice. This is a clear sign that the virus was actually altering the brain and therefore

their behavior. So why is this? How's this happening? Well, remember the blood-brain barrier that we just talked about? So what the researchers found was the virus that made the mice sick resulted in the production of something called an interferon. Basically, interferons are a group of signaling proteins, and they're released by host cells, and basically they're released in the presence of viruses. And what I mean by a signaling protein is it's effectively a way that the brain sends a message. The protein is released, and it's like transmitting a little packet of information. So in other words, these inferons, they send messages when you're sick. In other words, these inferons, they send messages when you're sick.

Now, what the researchers found is that the production of more inferon, in this case, stimulated receptor molecules that were a part of the blood-brain barrier, thus making it more likely that things could cross the barrier. In other words, the production of these interferons, which was caused by the mice being sick, changed some receptor molecules in the blood-brain barrier, and that made it more likely that things like the illness or parts of the illness could cross the barrier. So what does this mean? The research has compared the sick mice with genetically modified mice that didn't have receptor molecules. In animal research, this is quite common, especially with mice. They basically tweak the genetic makeup slightly so that the mice in this case don't have the receptor molecules

that the inferon activated. What the researchers found was that the genetically modified mice spent about half as much time floating as the depressed sick mice. So that's a sign that they were less depressed and that the virus wasn't able to cross the blood-brain barrier. And that's not all. The researchers found that the inferon response included the production of a molecule called CXCL10. Okay, I didn't name it and I don't know where they got that name, but that's what it's called, CXCL10. Anyway, the research team found that when more CXCL10 was present, it changes neuronal firing in the hippocampus and the amygdala. If you remember season one, the hippocampus is associated with memory formation and plays a key role in memory

formation. And the amygdala, as we've talked about so many times, is a key part of your emotional system. So this production of CXCL10 that was triggered by this increase in inferon, which was triggered by being sick, well, basically what it did is it impaired your learning system, and it also ramped up the emotional system. Now, that's a cellular basis for sickness and why we feel sick. But that's not all. A different research group examined human subjects and sickness behavior.

Now, I would not have volunteered for this study, because what the researchers did is they made their subjects briefly ill. They basically hooked them up to an IV and they added a solution, a lipopolysaccharide, to their bloodstream. And what that does is it does make you feel quite ill. But before this happened, the subjects were supposed to rate how they thought sickness would feel before and after they began feeling sick. So in other words, a one to 10. One meaning, you know, I don't think I'll feel that sick after this injection. Or 10 meaning, yeah, this is going to be really gross and I'm going to feel horrible. And what they found was fascinating. People who rated that they would feel only mildly sick

rated themselves as feeling more emotional distress after the injection than people who said they would feel very sick. So we've actually talked about this concept before because it occurs all across the brain. This is a prediction error. Now, if you remember when we talked about prediction errors the first time, a prediction error is when there's a difference between an outcome and expectancy. It's a very, very common term in learning. An outcome might be the result of a test you take or hitting a golf ball. And an expectation is your belief about how you would do. And if there's a difference between that outcome and that expectation, that's a prediction error. Now, in this case, there's a massive prediction error for the people that said they would only feel mildly sick. They were only expecting to feel

mildly sick. So when they felt more sick than they expected, their brain processed this as a violation of expectancy. And for the group that said they'd feel really sick, well, they did feel really sick. And therefore, there was no prediction error or a small prediction error. But what's really cool about this is it shows that sickness isn't just a cellular thing. This brings it to a very high level. So in other words, it shows that our perception of sickness influences how we actually feel. We call this top-down control. This is when the prefrontal cortex and the higher level parts of the brain are influencing the lower level parts of the brain. So they're actually modifying the

way the lower brain systems feel based on high level input. In this case, these prediction errors. And this influences brain function. This is why our brains don't respond well when we're sick. We've already said it influences the memory systems in the hippocampus, in the emotional systems, but it's also true for our decision-making systems in the prefrontal cortex. And it's even true for our motor systems. If you think back to season one, we did an episode about grabbing an apple. So even those systems in the supplementary motor area and the lateral premotor area, they're influenced when you feel sick.

Now, I thought I'd add one more because another version of sickness isn't a cold or a flu, but it's nausea. And nausea is a little bit different. Now, it's a bit of a complex story, but I'll walk you through it. Basically, there's a couple of different reasons why you might experience nausea. Well, one of the classic ways to experience nausea, which you might have had if you get motion sickness or you get sick on boats, is basic cerebellar inputs. So the cerebellum and the vestibular system, they basically are having problems processing motion. So you've got motion-induced nausea,

and that's happening in the cerebellum or the vestibular system. But you can also get input from the cerebral cortex, so the prefrontal cortex and these other high-level brain regions, and the limbic system, the emotional systems. And that means that there's cognitive and emotional input to nausea as well. This would be the feeling of nausea if someone tells you something really upsetting. So for instance, you find out a relative or someone that's close to you dies and you experience nausea. And there's also parts of the brain that they basically recognize different agents in the blood. So sometimes viruses and things like that can affect the bloodstream and the things that are in the blood. And this also basically contributes to feelings of nausea. So you can

get nausea from these sort of three main sources, from the motor system, the cerebellum and the vestibular system. You can get it from the cerebral cortex and the limbic system. So the first one was motion induced. The second one was more cognitive and emotionally induced. And the third one is things directly impacting the bloodstream. Now that all takes you to a very small part of the brain called the nucleus tractus solitarius. Basically, it takes in all of this information from various parts of the body and it integrates it. And what it does is it starts sending that out to the peripheral nervous system. So what happens is the vagus nerves get mediated. There's an increase in vasopressin levels.

The autonomic nervous system, which we've talked about in the past, is activated. And that gets you gastric dysarrhythmias. So that's the stuff in your bowels and your gut. And that all contributes to you feeling nausea. So it's a complicated story, but I hope you understood the walkthrough. Basically, there's sort of three high level things that interact with lower level systems. And that leads you to motion induced nausea, cognitive or emotionally induced nausea or nausea brought about by things influencing the bloodstream. Okay, that's the neuroscience of being sick. Now, thank you for listening, of course, as ever.

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That's one of our big goals for season three, which is coming up soon. And we have a website up, believe it or not. It's thatneuroscienceguy.com. It actually directs to my personal website, but there is a blog there. There's a link to the podcast and there's a link to the YouTube channel. We need to update that more. And we've got some really cool things coming for season three there as well. I'm going to apologize for yet another late release. You know, last week it was COVID or two weeks ago it was COVID. This week, it's me just having the common cold. And to be fair, life's a little bit busy right now. For

those of you that don't know, I'm a full-time professor running the Theoretical and Applied Neuroscience Lab. And every once in a while, I have to walk away from my love of podcasting and actually do my day job. Thanks for listening again, and we'll see you next week on the podcast.