NASA on the brain! Why Space Exploration Needs Neuroscience

Introduction

As NASA plans to return to the moon and eventually to Mars and deeper into space, scientists must carefully anticipate every problem to prevent future tragedies that would jeopardize human lives and the future of space exploration. The big unknown in this ambitious mission isn’t just the massive and incredible engineering feats required or managing dangerous CO2 levels. Rather, it is the psychological consequences that will befall the four brave astronauts who will live in a tiny capsule for approximately three years.

No astronaut has even come this close to spending this much time in space. Though astronaut Scott Kelly and cosmonaut Mikhail Kornienko have recently received a lot of press for spending a “year in space”, the total number of days was actually 340: just short of a year. The current record for longest single mission in space is 438 days, completed by Russian cosmonaut Valeri Polyakov in 1994 (1). In an interview, he declared that his healthy return to Earth proved that “it is possible to preserve your physical and psychological health throughout a mission similar in length to a flight to Mars and back.” This claim was misguided as Valeri had a very different experience than future astronauts will have. For one thing, he did not have to deal with interpersonal arguments that come with living with the same 3 cosmonauts for months at a time in a high-stress environment. Although he no doubt faced difficult periods of loneliness, different cosmonauts did rotate through and he wasn’t without human contact for his long mission. He also had much more protection from radiation than astronauts going to Mars will receive, and although 438 days is the current record, this pales in comparison to the current plan of a 2.5-3 year mission to Mars.

We clearly have a lot to learn before generalizing one cosmonaut’s experience to the future explorers who will venture into deep space. Although we’ve had a continuous presence in space for about 18 years, nothing about spaceflight is routine. So why would NASA even focus on studying the impacts of long duration space exploration on the brain and behavior? In the words of astronaut Scott Kelly,

“During my time in orbit, I lost bone mass, my muscles atrophied, and my blood redistributed itself in my body, which strained my heart.   Every day, I was exposed to ten times the radiation of a person on Earth, which will increase my risk of a fatal cancer for the rest of my life. Not to mention the psychological stress, which is harder to quantify and perhaps as damaging.”(2)

He’s not wrong: the microgravity, radiation, isolation and confinement characteristic of space travel can affect sensorimotor adaptations, cognitive ability, and neuronal structural integrity, in addition to sub-clinical psychiatric conditions. Using spaceflight analogs, we can attempt to study some of these deleterious consequences that threaten astronauts’ health and wellbeing as we prepare for exploration into the unknown. Part one of this article series will focus on how the vestibular system is affected by space and how increased radiation exposure can affect cognitive abilities.

 

Sensorimotor Considerations

Microgravity causes a fluid shift in our brain that confuses the vestibular system and causes extreme nausea, dizziness, and headaches for astronauts when they first get on the space station, in addition to when they return to Earth. The brain is a highly plastic organ that will adapt to different gravitational states easily. However, it takes time. When astronauts first land on Mars, there won’t be people to help them off the spacecraft and we can’t afford to waste time and money on a week-long recovery period as they stumble upon the Martian surface. To ensure that astronauts can successfully work as soon as they land, we need to understand how the vestibular system acclimates to different gravity states.

The incredible adaptability of the brain in space is demonstrated in a retrospective follow-up neuroimaging study, in which MRI data from 27 astronauts showed gray matter decreases in frontal and temporal poles and the orbits, as well as increases in sensorimotor brain regions (3). These structural changes signal that the brain is successfully adapting to a new microgravity environment. When astronauts arrive back on Earth, they often have to be carried out of the capsule and cannot stand. Their performance on a tandem walk test (often used during drunk driving tests as well!) is extremely poor. They feel nauseous and have terrible headaches. However, to illustrate that humans could be physically capable of walking and working on Mars after a long duration flight, cosmonaut Polyakov walked from the Soyuz capsule to a chair. In an interview, he explained how important this was:

“I was able to come out of the capsule by myself, to walk around, to undress, to dress, to do pretty much everything. And be conscious of everything. That was pretty much the goal of the flight. I had to show that it is possible to preserve your ability to function after being in space for such a long time. But the gravity on Mars is .37. And since I was able to stand up and walk on the Earth wearing a space suit, it shows that [a] human is able, will be able to stand up and walk on Mars.” (4)

This was an anomaly (an incredible one) but can’t be relied on as a standard for the astronauts travelling to Mars, especially as his mission wasn’t exactly analogous to a Mars mission will be, as outlined previously.

Scientists at NASA are now looking at training countermeasures to mitigate this sensorimotor dysfunction. One group has focused on a generalized Sensorimotor Adaptability (SA) training using variable (vs. blocked) practice sessions (5). This concept of interleaving, or “contextual interference” from cognitive psychology, is used to efficiently acquire skills that can be retained in the long term. This phenomenon shows that interference during practice, while negatively affecting performance in the short term, leads to superior retention and transfer performance in the long term and is surprisingly beneficial to skill learning. This was first seen in verbal learning (6) and then in motor skill learning (7),  and implies that performing in harder practice conditions leads to more effortful encoding and thus better long-term retention of skills.

Interleaving has been applied to many different skills and now can help with astronaut training. The scientists used different challenges in training so that subjects would generally improve their sensorimotor adaptability rather than improve on a single task.  Most SA training took place on a treadmill mounted on a motion base platform in front of a large screen displaying a visual scene that conflicts with the motion of the treadmill, so subjects must adapt rapidly to different levels of conflicting sensory environments. The researchers found that this SA training improved locomotor ability while increasing stability and lowering the cognitive and metabolic expenditure. Training methods using cognitive psychology principles will surely help us take our first steps on Mars.

 

Radiation

As we transition from low earth orbit to deep space travel, humans will be exposed to increasing harmful radiation. Solar particle events (SPE) and galactic cosmic rays (GCR) both contribute to the radiation effects that impact the central nervous system. In deep space and in transit to Mars, the dose rate of radiation is about 3 times more than that on the International Space Station (ISS). Increased radiation will undoubtedly affect physiological health, but out of all the risks posed by this elevated exposure, scientists know the least about how it affects the central nervous system both in-flight and later in life.

Experimental studies with mice and rats have shown that exposure to HZE nuclei (found in GCRs) at low doses significantly induces neurocognitive and operant deficits. Scientists found that cosmic radiation causes long-term cognitive dysfunction in mice as measured by the novel object recognition (NOR) task, Object in Place (OiP) task, and the temporal order (TO) task (8). These tasks can indicate changes in connectivity of the hippocampus and the medial prefrontal cortex. They found that irradiated mice didn’t engage in as much exploratory behavior for novel objects and didn’t show a recency effect. The mice were tested 12 weeks after radiation exposure, demonstrating the persisting deleterious effects that radiation has on learning and memory. After these surprising findings, the authors then tested rats 24 weeks after relatively low doses of radiation. Again, they found persistent cognitive deficits 24 weeks after, with no reduction in severity. In addition to these cognitive deficits, they observed significant reductions in dendritic complexity, spine density, and altered spine morphology in medial prefrontal cortical neurons. So, with chronic low-doses of radiation, comparable to what we might expect on a Mars mission (<0.5 Gray), there are radiation-induced structural neuronal impairments and cognitive impairments in spatial, episodic, and recognition memory as well as deficits in executive function and reduced rates of fear extinction and increased anxiety.  

HZE has also been shown to disrupt hippocampal neurogenesis in mice at low doses (9). In this study, mice were sorted into three groups: sham, acute (single exposure), and fractionated (chronic) irradiation. They found that relative to the sham exposure, both irradiated groups of mice had long-term deficits (3 months after exposure) in the number of proliferating cells in the hippocampal subgranual zone. Interestingly, they found no decrease in the number of adult neural stem cells, as expected. However, their results of decreased hippocampal neurogenesis have many unfortunate implications in learning, memory, and mood regulation impairments.

These animal models are crucial to understanding how radiation affects the brain without experimentally irradiating humans unethically. However, careful translation between animal and human models is essential as lifespan comparison and appropriate dosage amounts are still under debate.

Radiation experiments in humans must rely on cancer patients undergoing radiation or atomic bomb survivors, both are imperfect models with many confounding factors. For example, cancer patients undergoing irradiation have higher rates of chronic fatigue and depression (10). Deficits in neurogenesis may be the mechanism by which cognitive decline is occuring in irradiated patients since cognitive functioning and memory are closely associated with the cerebral white volume of the prefrontal cortex and cingulate gyrus (11). Additionally, a review on intelligence and the academic achievement of children after treatment for brain tumors reveals that radiation exposure is related to a decline in IQ scores, verbal abilities, and performance IQ as well as performance in reading, spelling, math, and attentional functioning (12). Thus, though we know that chronic radiation exposure similar to what is expected in an extended mission to Mars will affect the CNS, we don’t know exactly what the cognitive and psychiatric impacts will be and the degree of severity in which they will manifest.

 

Coming up...

Part two of this article series will explore some of the cognitive and mood impairments that manifest in space as well as different spaceflight analogs we can use to study these complex health impacts here on Earth.

 

 

References

1.     Schwirtz, Michael. “Crew in Moscow to Simulate Part of a Flight to Mars.” The New York Times, The New York Times, 30 Mar. 2009, www.nytimes.com/2009/03/31/science/space/31mars.html.

2.     Kelly, Scott. Endurance: a Year in Space, a Lifetime of Discovery. Transworld Digital, 2017.

3.     Koppelmans, Vincent, et al. “Brain Structural Plasticity with Spaceflight.” Npj Microgravity, vol. 2, no. 1, 2016, doi:10.1038/s41526-016-0001-9.

4.     Hall, Loretta. “Setting the Record: Fourteen Months Aboard Mir Was Dream Mission for Polyakov.” RocketSTEM, 11 Apr. 2018, www.rocketstem.org/2015/02/09/russian-cosmonaut-valeri-polyakov-spent-record-breaking-14-months-aboard-mir-space-station-in-1990s/.

5.     Bloomberg, Jacob J., et al. “Enhancing Astronaut Performance Using Sensorimotor Adaptability Training.” Frontiers in Systems Neuroscience, vol. 9, 2015, doi:10.3389/fnsys.2015.00129.

6.     Battig, W. F. (1966). Facilitation and Interference. In E. A. Bilodeau (Ed.), Acquisition of Skill (pp. 215-244). New York: Academic Press.

7.     Shea, John B., and Robyn L. Morgan. “Contextual Interference Effects on the Acquisition, Retention, and Transfer of a Motor Skill.” Journal of Experimental Psychology: Human Learning & Memory, vol. 5, no. 2, 1979, pp. 179–187., doi:10.1037//0278-7393.5.2.179.

8.     Parihar, Vipan K., et al. “Cosmic Radiation Exposure and Persistent Cognitive Dysfunction.” Scientific Reports, vol. 6, no. 1, 2016, doi:10.1038/srep34774.

9.     Rivera, Phillip D., et al. “Acute and Fractionated Exposure to High-LET56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis.” Radiation Research, vol. 180, no. 6, 2013, pp. 658–667., doi:10.1667/rr13480.1.

10.  Tofilon, Philip J., and John R. Fike. “The Radioresponse of the Central Nervous System: A Dynamic Process.” Radiation Research, vol. 153, no. 4, 2000, pp. 357–370., doi:10.1667/0033-7587(2000)153[0357:trotcn]2.0.co;2.

11.  Thurston, Jim. “NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States.” Physics in Medicine and Biology, vol. 55, no. 20, 2010, pp. 6327–6327., doi:10.1088/0031-9155/55/20/6327.

12.  Butler, Robert W., and Jennifer K. Haser. “Neurocognitive Effects of Treatment for Childhood Cancer.” Mental Retardation and Developmental Disabilities Research Reviews, vol. 12, no. 3, 2006, pp. 184–191., doi:10.1002/mrdd.20110.