Rachel Seidler: First of all, microgravity causes a range of physiological effects on the human body. So, sometimes it's hard to separate out what is learning how to move the body in this unusual environment and what is coming from the other physiological changes. So, just as an example, on Earth, gravity is pulling fluids down in our body. So, blood, and lymphatic fluids, all kinds of fluids in the body are pulled by gravity. We have a number of one-way valves in our bodies, and other mechanisms that keep blood pumping up towards the head, and when you go into space, gravity is no longer pulling on these fluids, so they tend to redistribute throughout the body. There's increased fluid distribution towards the upper body and the head.

For examples, some photos of astronauts show when they first go into space, they have this kind of puffy looking face in comparison to their Earth photos and that's because of this fluid redistribution, and this even happens in the brain. There's a shift in fluids in the brain. So, it can be difficult to tell are some of the effects that we see on behavior mediated, for example, by changes in fluid distribution in the brain or just learning how to move the body when the limbs are unloaded, they're kind of floating, you have altered sensory inputs as well. The vestibular system in the inner ear tells the brain how the body is oriented with respect to gravity. Are you upright? Are you leaning forward? And that system works, as well, by gravity pulling fluid around in the inner ear, and you don't have that in flight. There are all kinds of things that are affecting how people move and how people function in microgravity, so sometimes it's hard to figure out what the exact mechanisms are for any behavioral changes that we see.

Jesse Lawler: I was reading something recently about how whether a person sleeps face-down or face-up, or on your side. That seemingly innocuous choice can actually make a difference in the lymphatic system and how much cerebral plaques are cleared out of your brain while you're asleep. I think it is easy to forget that the circulatory system has a heart pumping things around. But, for the lymphatic system we're really just waiting for gravity and or the random motions of the body to kind of keep things moving, get things flowing along, which probably makes physical exercise even more important for astronauts.

Rachel: Yes, I think that would be the case and if you think about how you get garbage, if you will, out of the brain, that is happening through cerebrals spinal fluid and, potentially, lymphatic system, and this stuff turns over when you sleep. Sleep is also disrupted in flights, so not just the orientation of how you sleep, but sleep itself. These poor guys are working outside of their normal circadian rhythm, so sleep can be quite difficult.

Jesse: I know that another one of the confounding factors, and something that might be difficult to study is the extra amount of rays, whether that's Gamma rays is or something else that might be going through an astronaut's body, which is something else that you don't deal with here when you're protected by Earth's atmosphere. How do you try to slice and dice and find out what effects are driving from what sources?

Rachel: If you're asking about radiation, and rays, and so on, in low Earth orbit, the space station will still be generally pretty well-shielded. Of course people, wear radiation count tags so that can be tracked when they're in space. But, radiation, I think, will certainly be more of an issue when we're talking about more deep-space missions of the future. For example, sending someone to Mars, that would be a real concern.

But, in terms of trying to parse out the multiple inputs, one thing that we've been able to do that I think will really help us interpret our data in the long run is we have run the same experiments in a long duration bed rest environment. NASA really likes these space flight analog environments. For example, they study people wintering over at an Antarctic field station, for example, to see how people deal with being in a small enclosed environment with the same people for a long period of time. They also do experiments where they put people on bed rest.

We've done a bed rest study where healthy people were on bed rest for 70 days and their head was tilted six degrees below their feet. So, this is going to mimic several aspects of the microgravity environment, including the fluid shift towards the head, the unloading of the body, particularly the lower limbs. But, it's not affecting the vestibular processing of gravity, because gravity is the same on Earth if you're lying down versus standing up. Maybe you've rotated the orientation of the gravity vector, but it's still present. Or, you've rotated the body with respect to gravity.

So, we will eventually compare those data that we collected in bed rest with the ones that we're getting in space flight so we can see where there are similarities and where there are differences. In places where there are differences, then we can start to speculate about whether those effects might be mediated by vestibular changes, or by other aspects that are unique to the space station environment as opposed to bed rest on earth.

Jesse: That sounds just like a torturous experiment to be face down in bed for 70 days as a healthy person.

Rachel: Yeah. There's some interesting blogs about this. In fact, a couple of the subjects in our experiments kept a blog with some photos, but I think the environment is pretty tough on them. They can prop their head with their hands for a few minutes at each meal, but they otherwise do not lift their head, and they do not get out of bed. For example, they're taking supine showers, they're using a bed pan, if they're on a laptop or watching a movie. It's in a frame above the bed, but they do certainly get paid a lot.

Jesse: What do you see happening to people physiologically over the course of that time? I imagine there's just a ton of changes.

Rachel: In our bed rest studies, we measured several measures of cognitive function, sensory motor function, and then also brain changes. Interestingly, the sensory motor changes that you see, in many ways, mimic what you see with space flight. So, for example, balance is disrupted when they get out of bed, functional mobilities like navigating an obstacle course is disrupted, and part of this, of course, can be tied back to muscle weakness and inactivity.

But, part of it also seems to come from modifications in sensory integration and sensory re-weighting. What that means is when you move around in your everyday life, you rely on vision as well as this vestibular system in our ear, as well as proprioception, which is the sensory input that tells you where your limbs are relative to your body, and where your body is in space, how much your body weighs etcetera. Normally, you integrate all of those together in your brain to form this integrated view of where your body is in space.

Now, in space flight, in microgravity, that gets changed quite a bit, because the brain realizes these vestibular inputs are unreliable or unusual, so it starts relying more on vision and proprioception. It downweighs vestibular input, and interestingly, in bed rest, we see some re-weighting as well. So, there seems to be at least roughly similar adaptation processes in terms of sensory integration both in flight and in bed rest. We can see that in terms of some of the changes that we see in the brain.

So, with bed rest, we see, similar to what we saw with space flight, an increase in gray matter volume in the part of the brain that controls the lower limbs, or the legs, and that processes sensory information from the legs. You can imagine in both environments, you're really not using your legs in the same way that you do in everyday life. Even though we don't think about it, when you're just standing still, the large muscles in your legs are contracting to resist the effects of gravity, otherwise we would just crumple.

We're using these muscles all day every day, and to suddenly stop, the brain is kind of remodeling to deal with that big change in function, and what we think is happening with the enlargement of these regions would be that imagine you're trying to kind of increase the gain of the system. So, the proprioceptive inputs that the brain is getting are much, much smaller than what it is used to. So in a way, the brain is trying to turn up the volume on these inputs, and is adapting, over time, to try to learn how to process that information.

Jesse: There's sort of that famous example of brain plasticity where, if people go blind in an accident, then basically their other senses can kind of step up their game, pick up some of the slack, and one of the ways that that happens within the brain is by actually reallocating some of the processing power of the visual cortex to go to other sensory inputs. Do you see anything similar happening with the motor cortex getting reallocated for these people that are not exercising their bodies physically, where maybe some of the parts of their brain that normally would be used for skeletal muscle movements are given to other things, other processes?

Rachel: That's a great question. We don't really know the answer, at least for space flight at this point, because the paper that we published recently comes from retrospective MRI scans, and these are just pictures of brain structure. We are able to look at how the structure changes from pre to post-flight and to try to correlate that with changes in balance, but there aren't a lot of measures or variables that are available in that data set. We are, right now, running a prospective study. We're about halfway through or a little bit more. We're getting a lot of different measures of cognitive function, sensory motor function, and not just brain structure, but also brain function.

One that I'm really interested in is looking at functional representations in the brain of vestibular cortex. This means having someone lie in the MRI scanner and recording functional brain activity while we're stimulating the vestibular system. Because that system changes so much with flight, we know that there are lots of behavioral effects on behaviors that are mediated by the vestibular system. So, balanced spatial orientation, eye-head coordination, that's one that I'm really interested in looking at how the brain kind of remaps processing a vestibular inputs, if you will, from pre to post-flights.

We can start looking at more functional plasticity measures, like what you're alluding to with the studies on people who go blind. They've even shown these studies in people who volunteer to wear a blindfold just over the course of five days, and they have them learned to read braille during this time, and they show that the brain starts processing these tactile inputs for braille reading in the visual cortex just over the course of five days. So, it's really fascinating stuff. This really is why I'm so interested in looking at brain plasticity with space flight.

You imagine, if someone comes to my laboratory at University of Michigan, and I'm looking at brain and behavioral changes with learning new motor skills, maybe I could get them to practice an hour a day, maybe I could get them to come back a handful of times, or three times a week for a month, something like that, but they're going to start to get bored, and they're not going to want to come back and spend all that much time. But, imagine people who go to the space station, they are exposed to this microgravity stimulus 24 hours a day for six months, or even a year in the case of the recent one-year mission. There's basically no escaping it, so they are adapting around the clock, and for me, this is extremely fascinating for being able to study the brain's maximum capacity for adaptation and neuroplasticity in a healthy brain. I mean, we could study this on earth with people maybe adapting to a catastrophic injury, or adapting to a disease, but then we're not looking at adaptation in the context of the healthy brain.

Jesse: In a 70-day study, on the one hand, 70 days seems like a really long time, but on the other hand, you could kind of imagine that changes might continue even beyond that point. As you're looking at those changes, do you see a bunch of changes at the beginning, and then that kind of levels off, or are there continuing changes throughout that period?

Rachel: During the 70 days, we measured people roughly one week in, and then a little over a month, and then at the end. So, we have kind of three time points of our measurements throughout that 70 days, which means that the temporal dynamic measurement is a little bit coarse, but we really see two types of changes: one that we would call gradual accumulating changes. So, across these three time points, there seems to be a steady change in some of our measures, but some of our measures show very fast changes. So, changes that are evident at our first time point, and that then level off.

This suggests that there's at least two different kinds of adaptive mechanisms that are taking place that are operating on different time scales, and this will be very hard for us to measure in space flight. Of course, there's not an MRI scanner on the International Space Station, so we're not taking our brain measurement at multiple time points. We do have the crew members doing a subset of behavioral tests while they're up there. They're able to do some of our tests on a laptop and we're able to look some of those dynamics: what's the time course of behavioral changes? But, the brain changes we'll just be able to look at, for example, magnitude of change from pre to post-flight, how does that correlate with behavior changes, and then also, I think, a very important question, because no one has looked at this yet is what's the time course of recovery of any changes that we see?

There have been decades of experiments measuring changes in behavioral functions. We know that after the astronauts are back on Earth for a few weeks to a month, they readapt to moving in earth's gravitational environment. They don't get cleared to drive a car right away. They have to go through a couple of weeks of physical therapy, but what we do not know is whether that means the brain has recovered. So, there could still be persisting, for example, compensatory changes in the brain, or you could have substituted brain networks from pre to post-flight in order to perform the same behaviors. This is kind of a risk assessment study as well as study about brain plasticity.

Jesse: Have there been any interesting anomalies or outliers for people coming back on to Earth and reacclimating to Earth's environment either particularly good or particularly bad reintegrators onto Earth?

Rachel: So, when we look at people readapting after they've been in space, it's kind of interesting to think about what that means. So, someone who adapts better while they're in microgravity, they adapt more thoroughly, or perhaps they have more retention of that adaptation, is actually going to have the most difficulty when they come back, right? Because they've adapted so well to microgravity, they have maladaptive motor control for Earth's gravity.

One thing that has been observed by a number of different scientists studying space flight adaptations is that there's a huge range of variability in terms of how people readapt when they come back, and this is a very interesting question to think about. First of all, why? Why do some people recover faster than others? Does this mean anything about how they adapted while they were in space? Is there anything we can do to perhaps identify slow or poor adapters ahead of time so we can give them more support in terms of adaptive training pre-flights? My collaborator, Jacob Bloomberg, at Johnson Space Center has a large set of experiments on adaptive training. Can you train people for flight ahead of time?

The other reason that this is an interesting question is when people return to Earth, again, they're engaging in a lot of physical therapy and trying to relearn how to maintain their balance, coordinate eyes and head so they can do everyday things like drive a car. So, now imagine what would happen if or when we send someone Mars, which has a partial gravity environment which is different from Earth and different from what people will experience on their way there, if we have someone who is not going to adapt very well when we get there and they're unable to, for example, drive a vehicle around for their first few weeks, what does that mean in terms of their ability to complete a mission, and also for their own safety? For example, if they needed to rapidly escape from a vehicle, for example, upon landing. So, that's a very important question: why do some people adapt and readapt faster than others? We don't really know the answer at this point. All we know is that the variability is extremely large.

Jesse: I don't know. I assume that we've kind of had that problem almost solved. Here on Earth, we have the Google cars. Self-driving cars probably will be a thing within the next five years, and I assume with NASA's budget having a self-driving rover can't be that much to ask.

Rachel: Right. I guess we could hope so but again, something like, if there is, imagine, some sort of crash landing and a hatch that was maybe supposed to open automatically can't open, and now someone has to keep their balance, and do some heavy lifting, and walk or run from a vehicle, that may be problematic. But, I like the idea of the self-driving rover.

Jesse: What do you see as far as psychological changes in the astronauts? I assume it's hand-in-hand with the motor cortex changes and perceptual changes, there's going to be psychological changes, if nothing else, going stir crazy.

Rachel: Right. So, there are, I would say, maybe a couple of different categories of psychological changes, and one that we are measuring is more cognitive function. So, things like short-term memory, processing speed, attention, and these things have been studied a little bit in the space flight environment. For example, we know that dual tasking is an impaired in space sight. There seems to be, perhaps, more neural resources that are allocated just to the adaptation process itself. So, doing two things at the same time might get slowed down.

Then, there are a lot of these interesting anecdotal reports from crew members experiencing something that they call space fog. So, this is just feeling a little bit out of it, not being able to pay attention, and I think finding the appropriate measures to capture that has been difficult. There are number of groups trying to measure cognitive function and cognitive abilities in space.

The other category of psychological function that you could think about would be mood and well-being, even team dynamics, or what it's like to be missing your family, and there certainly experiments about that as well. Crew members, as well, are provided with psychological support. They have counselors on earth that they can call and communicate with when they need. Things are apparently much better these days with more access being able to communicate with families. You may know many astronauts even have Twitter feeds.

Jesse: Yeah, I subscribed to a few of them. They get great photos there.

Rachel: They're really fun, aren't they?

Jesse: Yeah.

Rachel: So, there's a lot more capacity for communication with friends and family while you're up there. But, one thing that's very interesting about those measures in space, and this has also been seen in experiments conducted with those Arctic winter over experiments that I mentioned, where you get this initial high mood: you're in an exciting place, you're accomplishing a mission, you're working on something that you've trained for for quite a long time. But then, these mood measures start to deteriorate. I think they reach a low in roughly the third quarter of a mission.

Jesse: Is that third quarter time-independent of the length of the mission or...?

Rachel: It seems to be independent of the length of the mission, and you can imagine, as well, there may be some problems with team dynamics. "I just can't stand the way so-and-so chews their food, and I have to eat with them every day, and they irritate me when they do this." These conflicts become harder and harder to escape from.

Jesse: You cannot kick your roommate out when you're on the International Space Station.

Rachel: That's right. Or, in these arctic field stations, you can't leave for a period of several months. You're locked in for the winter. But, fourth quarter, there's a big rebound in mood, and this is where, maybe, it makes sense in terms of it's not really tied to mission duration. But, at that point, you know you're going home. It's tangible, it's within reach, you know when you're going home, and people are starting to look forward to that. It's interesting though, one of the, anecdotally, that I and others have heard from a large number of crew members is that they would go back in a heartbeat if they could, or they would stay longer, if they could. Despite those statements, there still seems to be a little bit of this third quarter mood slump and fourth quarter mood recovery.

Jesse: How many people do make multiple trips into space? Like, if you go into space once, what's your chance of going into space again?

Rachel: Pretty good. For example, a lot of subjects in my experiments are repeat flyers. It might be their second, third, or even their fourth mission. Particularly, people who may have been involved in the space shuttle era, there, the missions were pretty short. They were just a few weeks. You can imagine, if you've put someone through all of this training, and they've been successful in this environment, it's a pretty good investment to send them again.

You know, it's interesting, there were some initials anecdotal reports suggesting that there could be some learning to adapt. So, people who had been more than once might adapt more quickly. But, now that more data have been accumulated, that effect seems to have maybe been watered out. I'm saying maybe because I haven't yet seen a paper published on this. I've only seen presentations here and there. But, I think that's a really interesting question as well. Can you learn to learn how to move in microgravity?

Jesse: Hearing you talk, it makes me wonder what a space virtuoso would look like. Somebody like what Mozart was to music or Isaac Newton was to mathematics, somebody that's profoundly well adaptive to the space environment, if we've had enough humans in space to even see that or recognize that what that might look like.

Rachel: Yeah, that's a good question, and I don't know. At least from what I've seen at conferences and papers, I haven't seen anything published or presented about a super-adapter. I guess we could imagine it might be someone who goes up into space, and they have little or no trouble with motion sickness. You do get space motion sickness. Again, you can credit this to the vestibular system. Maybe someone who sleeps well, who doesn't feel fatigue, who maintains a high level of cognitive performance, maybe good team dynamics, good mood, and then comes back and readapts quickly. If we could bottle resiliency, it would be great not just for this context, but for quite a few contexts in life.

Jesse: I know that it's not technically correct to call it the 10,000-hour rule, but that's what most people know it as: the idea of getting intense deliberate practices, something to get really good at it. Is there anything that, once a person is up in space, they're recommended to work on to kind of build their space aptitudes while they're in that environment?

Rachel: That's an interesting question. Of course, there is extensive training before they go on a range of things. They're practicing in a neutral buoyancy lab underwater wearing a space suit and those large gloves that you see people wearing on space walks so they can practice manipulating a wrench, they're flying in jets, they are learning instrumentation panels, they're learning Russian, because their transport vehicle, these days, is the Soyuz rocket, and of course, they want to be able to communicate well with cosmonauts while they're up there.

Then, while they're up there, I know that there is some sort of booster training of refresher training, but this tends to be more for mission-relevant task. For example, you maybe have a task that you have to accomplish sometime while you're up there, but it's only a one-time thing, and maybe you've been up there for two months, and you might not remember, quite as well, the training that you received on the ground. What several crew members will do is make a video of themselves doing the training, and then they can watch it on their iPad while they're up there as a refresher right before they do the task.

Now, as far as stuff they might be doing to help them adapt more quickly when they come back, one really big thing is exercise. Astronauts are typically exercising close to two hours a day, and this is either they're bungeed to a treadmill, or they're on a stationary bike, they're using of some form of resistance equipment. Several studies have shown that this really helps in terms of protecting bone density, muscle mass at least to some extent, certainly in comparison to doing nothing.

But, one thing that it really doesn't help with as much are these vestibularly-mediated behaviors. So, things like balance, eye-head coordination, and one thing that's been discussed recently is whether there's something that we can provide to crew member on the station that might provide balance training. So, even if you're working on the treadmill, you are bungeed in place. Otherwise, of course, you would float off when you push on it, but then that means there's not much of a balance requirement for trying to stay upright.

I don't know if you could imagine some sort of balance stability ball - you know, those half balls that you see people standing on at the gym or a rocker board, a wobble board, if there's some way to get that to work in the microgravity environment, that that might be something useful, particularly if you could integrate it with the current exercise systems.

Jesse: I've got to ask, just going back to the earlier study that you did with the people that are lying prone for 70 days, how much are they paid to do that?

Rachel: I honestly don't know, because this is something that NASA takes care of, and then once they get that campaign set up, so they get people in the same place on bed rest, then they provide a lot of support for them. There's a dietitian, there's round-the-clock nursing staff just to make sure everybody is okay. Then, what they do is they solicit proposals from multiple investigators.

For example, while I'm doing my study on these people, there are a whole range of other studies that are being conducted looking at things like bone density, or blood measures of hormonal changes, or measures of fluid shifts, studies of psychological stress and journaling, or tests of, perhaps, an intervention, maybe a drug that might combat reduced bone density. They certainly try to get a lot for their money out of these people. They're kind of professional guinea pigs during this period. But, I think if you Google it, you could find an advertisement to see how much they get paid.

Jesse: Okay, this is Jesse interjecting from the future here, but the answer to this question is 18,000 U.S. dollars for 70 days of mandatory prone bed rest, and now returning to the interview already in progress.

Do we have enough information yet about when people are going out into deeper space, whether that would be on one of the moon missions or on a theoretical Mars mission that we would have in the future what the amount of extra radiation that they would be exposed to, what some of those effects might be?

Rachel: I don't think we have quite enough information yet, but there are a whole host of studies, experiments that are being conducted to investigate this, and studies looking at radiation effects on human physiology and animal physiology has been conducted for quite some time. Radiation is dangerous, but also it certainly used as a medical treatment in some cases. But, what has not been studied quite as well is the effects of the specific types of radiation that people would be exposed to in space. They're quite different. The doses are different, the rays themselves are different, and so there are experiments being conducted right now, and in the last few years.

I know people are quite concerned about trying to close the loop on that a little bit in terms of not only what are the effects, but also what can you do about it? How can you shield people in the vehicle, or can you provide them with a countermeasure, whether it's a food, or a beverage, or a pill, something that will help to offset some of those effects? I think this is a really interesting environment to study how to impact human physiology and to think about human space exploration as one of our last frontiers.

Sometimes people ask me: why would you study humans in space? Why can't we just send robots and probes? But really, I think this is a huge part of human nature is for us to explore our environment, and I think our environment extends much further than it has in the past, and I think it's really incredible to get people out there exploring space beyond our own planet, and being able to understand the impact that has on the body is bringing us a step closer towards making it more accessible for more people.

I'm sure you know there is a burgeoning space tourism industry, and the plans are certainly not to send people for very far or for very long, but you could imagine that changing in the future, and I think it's just a very exciting topic. It's an exciting time to be working in this field.

Jesse: What do you think that we'll know in five years that we don't know now? Conversely, what do you think that we definitely won't know in like 15 or 20 years that it would still be good to know?

Rachel: This is a tough timeline, because if you think about sending people to the space station, we're not sending very many each year - it's just a handful - and then they're up there for six months. So, if we really want to study them, you're talking about maybe a six-month lead-up time for multiple pretesting to get some sort of stable baseline, then they're gone for six months, and then you want to study their recovery. So, five years, we're talking about experiments that are already right now.

Those are the experiments that we're doing, looking at brain and behavioral changes with flight, there are several interesting studies looking at cognitive changes with flight, several interesting studies being conducted on Earth about radiation, what can we expect to see with the doses of radiation that you might be talking about. If you send someone to Mars, or to lasso an asteroid, or any of the other sort of deeper space missions.

But, 15 to 20 years, so now we're talking about a much larger time frame to work with, and I think some of the important really questions that we will want to have answered to that point are not just radiation risks and countermeasures that are trying to get a really good handle on vestibular countermeasures that can be done while someone is in space, so that if we put them down on Mars or somewhere else, they can be ready to go right away, but also this question of dose response changes.

So, if we send someone for six months versus if you send someone for one year or two years, if we're talking about sending someone to Mars, it's going to be at least two years round trip, and you want them to spend some time there. I think it's really important to know, is there a point of no return where if someone's in a microgravity environment for two years, do they drop off a cliff in terms of their bone density or fluid distribution? This is a really unexplored question that I think will be really important to answer, and that's the kind of thing that I can see we could answer in the next 15 to 20 years.

Jesse: Have you or any other researchers, to your knowledge, tried vibrating people that are in these environments? Like, I know they have got some devices where you can stand on something that's vibrating, and I think you can even change the oscillatory rate. But, it seems like that might be interesting to kind of shake up some of the lymphatic fluid within a person. Has anybody looked at that?

Rachel: That's an interesting idea. I don't know if people have looked at it for those effects, so you could maybe imagine, you might wonder, I do not know, if it might impact bone density, or something that's a little bit outside my range. One thing I can say that interest has been up and down over the years about this, but for example, artificial gravity. So, if you put some on in a giant centrifuge, you can create an artificial gravity environment, and that would be beneficial for the fluid system, for the bones, maybe for the muscles as well. So, there are some resurgence of interest in that as a potential countermeasure. Of course, that's difficult to implement in space. It would be something heavy, something costly to incorporate into a station or a ship. But, that topic is now becoming popular for discussion again. So, I don't know if we'll see something like that in the future or not.