STEM Today by Abhishek Sinha

STEM TODAY March 2019, No. 42

CONTENTS CBSÂSM6.1: Determine if sensorimotor dysfunction during and after longÂ duration spaceflight affects ability to control spacecraft and associated systems

Sensorimotor disturbances associated with spaceflight can lead to decrements in the ability to acquire information from instrumentation and spatial disorientation leading to performance and safety issues. It is necessary to determine if a crewmember can land and operate a vehicle after long duration spaceflight. This gap needs to be placed in the context of the expected operating environment of future vehicles. Design of future vehicles should account for human factors in the cockpit and task design to avoid provocative movements or physically difficult tasks.

Editorial Editor: Mr. Abhishek Kumar Sinha Editor / Technical Advisor: Mr. Martin Cabaniss

STEM Today, March 2019, No. 42

Disclaimer ( Non-Commercial Research and Educational Use ) STEM Today is dedicated to STEM Education and Human Spaceflight. This newsletter is designed for Teachers and Students with interests in Human Spaceflight and learning about NASA’s Human Research Roadmap. The opinion expressed in this newsletter is the opinion based on fact or knowledge gathered from various research articles. The results or information included in this newsletter are from various research articles and appropriate credits are added. The citation of articles is included in Reference Section. The newsletter is not sold for a profit or included in another media or publication that is sold for a profit. Cover Page Argentina, Chile and the Andes mountains iss058e006004 (Jan. 26, 2019) – This photograph of South America from bottom to top looks from the northeast coast of Argentina to southwest across Chile, the Andes mountains and the Pacific Ocean. The International Space Station was orbiting 259 miles above the Atlantic coast of the South American continent. Image Credit: NASA

Back Cover Baja California and Mexico Dust clouds blowing out of Mexico across an otherwise cloud-free view of Baja California The natural-color images required to make this oblique view were acquired on November 27, 2011, by the Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA’s Aqua satellite. The Ocean Color Team at NASA Goddard processes images like this to help assess the presence of sediment and plankton in the sea. Dust storms interfere with that processing, as the sandy aerosols block much of the incoming sunlight and the outgoing, reflected light. Dust storms can disturb human activity on land, but once they blow out over the Gulf of California and Pacific Ocean, they help fertilize the waters with nutrients that promote phytoplankton blooms. In winter, the waters around Baja are often full of whales, as the largest creatures in the sea often eat the smallest plankton. November 27, 2011 Image Credit: NASA

STEM Today , March 2019

Editorial Dear Reader

STEM Today, March 2019, No. 42

All young people should be prepared to think deeply and to think well so that they have the chance to become the innovators, educators, researchers, and leaders who can solve the most pressing challenges facing our world, both today and tomorrow. But, right now, not enough of our youth have access to quality STEM learning opportunities and too few students see these disciplines as springboards for their careers. According to Marillyn Hewson, "Our children - the elementary, middle and high school students of today - make up a generation that will change our universe forever. This is the generation that will walk on Mars, explore deep space and unlock mysteries that we can’t yet imagine". "They won’t get there alone. It is our job to prepare, inspire and equip them to build the future." STEM Today will inspire and educate people about Spaceflight and effects of Spaceflight on Astronauts. Editor Mr. Abhishek Kumar Sinha

Editorial Dear Reader The Science, Technology, Engineering and Math (STEM) program is designed to inspire the next generation of innovators, explorers, inventors and pioneers to pursue STEM careers. According to former President Barack Obama, " Science is more than a school subject, or the periodic table, or the properties of waves. It is an approach to the world, a critical way to understand and explore and engage with the world, and then have the capacity to change that world..." STEM Today addresses the inadequate number of teachers skilled to educate in Human Spaceflight. It will prepare , inspire and educate teachers about Spaceflight. STEM Today will focus on NASA’S Human Research Road map. It will research on long duration spaceflight and put together latest research in Human Spaceflight in its monthly newsletter. Editor / Technical Advisor Mr. Martin Cabaniss

STEM Today, March 2019, No. 42

Human Health Countermeasures (HHC) CBS-SM6.1: Determine if sensorimotor dysfunction during and after long-duration space ight a ects ability to control spacecraft and associated systems Sensorimotor disturbances associated with space ight can lead to decrements in the ability to acquire information from instrumentation and spatial disorientation leading to performance and safety issues. It is necessary to determine if a crew member can land and operate a vehicle after long duration space ight. This gap needs to be placed in the context of the expected operating environment of future vehicles. Design of future vehicles should account for human factors in the cockpit and task design to avoid provocative movements or physically di cult tasks.

Eye-Head Coordination in 31 Space Shuttle Astronauts during Visual Target Acquisition

In 1989, the NASA began a program to progressively lengthen Space Shuttle missions from 4 days to 17 days, and plans included missions of up to 28 days. Part of this program included a series of investigations to assess crew performance during and after the critical phases associated with Space Shuttle landings. Using data obtained during the first 24 Space Shuttle missions, investigators determined that the primary concerns were orthostatic intolerance and neurovestibular deficiencies. Despite intensive simulator training, some Space Shuttle commanders and pilots were unable to land the Shuttle with the desired performance specifications after short (less than 8 days) missions. Because the crew would continue to land the vehicle manually, keeping the autoland capability for an emergency backup only, landing proficiency was anticipated to degrade even more after extended Space Shuttle missions. However, no data was available to determine whether changes in landing proficiency might be related to the length of time spent in the microgravity environment.

STEM Today, March 2019, No. 42

The objective of this study was to assess how astronauts perform a visual task that was required to pilot and land the Space Shuttle. Authors measured the eye and head movements of pilots as they acquired specific visual targets in the horizontal plane before and after they participated in a Space Shuttle mission of 6 to 17 days. If pilots are unable to adapt their eye-head coordination to the changes in gravitational environment they will have difficulty acquiring information from instrumentation or will have delays capturing visual targets. The risk is greater in situations that require constant vigilance, timely responses, and accurate visual target identification and/or location, such as during a Space Shuttle landing. On final approach for landing, the Space Shuttleâ&#x20AC;&#x2122;s speed exceeded 300 knots, and it descended nearly 53 m in altitude and traveled more than 145 m downrange during the time required for the pilot to acquire a single target displaced 30â&#x2014;Ś to 60â&#x2014;Ś from straight ahead. Therefore, there was concern that a delay in visual target acquisition might compromise the safety of crews on short-term as well as extended-duration flights.

Previous reports have documented modifications in eye-head coordination during visual target acquisition and decreases in ocular saccadic performance in astronauts after they return from short duration spaceflights. However, for these previous studies, data was collected one or two days after landing and the studies involved a very small number of participants. Authors were able to collect data just a few hours after landing (on R + 0) from 31 astronauts, most of whom were Space Shuttle pilots. This larger number of participants allowed them to assess whether a correlation existed between the astronauts’ performance and the duration of their spaceflight. Subjects participated in one of 17 Space Shuttle missions lasting 6 days to 17 days. Eight subjects participated in one of 6 missions lasting from 6 to 9 days (mean 8.4); 14 subjects participated in one of 6 missions lasting from 10 to12 days (mean 11.0); and 9 subjects participated in one of 5 missions lasting from 14 to 17 days (mean 15.0). As shown in Fig. 1, flight duration increased progressively during the Extended Duration Orbiter Program, starting with STS-36 (4.5 days) and culminating with STS-72 (17 days).

STEM Today, March 2019, No. 42

The investigation presented here began about 18 months into the program and was conducted from November 1991 to January 1996. The visual target acquisition experiment was one of 4 protocols to investigate changes in visual-vestibular interactions as a function of exposure to spaceflight: visual target acquisition, gaze stabilization, pursuit tracking, and sinusoidal oscillations. The crew members were tested at 3 different times before flight and 3 different times after the flight. Preflight testing took place at the NASA Johnson Space Center 120 days before launch, 30 days before launch, and 10 days before launch. Early post-flight testing was performed on the landing site (either at NASA Kennedy Space Center or at NASA Dryden Space Research Center) within 2 hours of wheels stop (R + 0). Post-flight testing was performed again at NASA Johnson Space Center 2 days after landing (R + 2) and 4 days after landing (R + 4) to track recovery to baseline. Results Eye-head coordination While acquiring images 20◦ and 30◦ off center in the horizontal plane, the eyes and the head make one single movement to the target. The head, having greater inertia than the eye, typically moves after the eye has moved in the orbit. Gaze is the direction of the visual axis with respect to space, which is defined as the sum of eye position with respect to the head, and head position with respect to space.

At the end of the eye saccade the gaze has already reached its final position, but the head continues to move.

The head movement stimulates the horizontal semicircular canals and produces an eye movement through the vestibulo-ocular reflex that is opposite in direction and velocity to that of the head. When moving to a target that is offset 60◦ , the gaze often undershoots the target by 5-10◦ and a corrective eye saccade occurs to reposition the gaze onto the target. In general, the total gaze movement is greater than the total head movement, so that the final position of the eye is offset in the direction of head movement. Comparison of the recordings obtained before and immediately after flight indicated that the amplitudes of the initial eye saccade and head movement were smaller and the duration of gaze movement to the target was longer after flight than before flight (Fig. 2).

STEM Today, March 2019, No. 42

Gaze latency The delay between the start of the eye and head movements after flight (R + 0: 24.9 ± 32.4 ms) was not significantly different from the delay before flight (19.4 ± 25.6 ms), when the subjects took 350 to 440 ms to reach the target. This gaze latency increased as a function of the angular position of the target (Fig. 3). The effects of spaceflight on gaze latency were analyzed using a 3 targets (20◦ , 30◦ , 60◦ ) X 4 sessions (Pre, R + 0, R + 2, R + 4) repeated-measures ANOVA, alpha = 0.05.

There was a significant effect of target position [F(2,360) = 29.74, P < 0.001] and a significant effect of spaceflight [F (3,360) = 2.76, P = 0.04] on gaze latency, but no significant interaction between target position and spaceflight [F (6,360) = 0.05, P = 0.99]. An increase in gaze latency was observed in more than two-thirds of the subjects on R + 0. The largest increase relative to pre-flight latency was 172 ms. When averaged across all subjects, the gaze latency for reaching the 30◦ and 60◦ targets increased relative to pre-flight latency by 34 ms (P = 0.024) and 30 ms (P = 0.006), respectively. Responses had returned to baseline on R + 2. Eye and head velocity The time to bring gaze on target is determined by the maximal eye and head velocities. Before the flight the mean peak velocities of the initial eye saccade were 363.4◦ /s (SD = 54.7), 374.6◦ /s (SD = 60.7), and 382.3◦ /s (SD = 68.1) for the targets at 20◦ , 30◦ , and 60◦ respectively (Fig. 4A). A two-way repeated-measure ANOVA indicated a significant effect of spaceflight [F (3,360) = 6.91, P < 0.001] on peak eye velocity, and no difference between the targets [F (2,360) = 1.02, P = 0.36]. On R + 0, the peak

eye velocity when acquiring for the 30◦ and 60◦ targets decreased relative to pre-flight peak velocity by 26.0◦ /s (P < 0.01) and 36.4◦ /s (P < 0.01), respectively. Responses had returned to baseline on R + 2. The peak head velocity was related to position of the target; the more offset the target, the faster the head movement (Fig. 4B).

STEM Today, March 2019, No. 42

A two-way repeated-measure ANOVA indicated a significant difference in peak head velocity between the targets [F (2,360) = 256.3, P < 0.001] and a significant effect of spaceflight [F (3,360) = 4.50, P < 0.01]. On R + 0, the peak head velocity when acquiring the targets at 20◦ , 30◦ , and 60◦ decreased relative to pre-flight peak velocity by 10.0◦ /s (P < 0.01), 6.9◦ /s (P < 0.02), and 6.7◦ /s (P < 0.05), respectively. On R + 2, the peak head velocity was still significantly slower than preflight peak velocity (P < 0.02) when acquiring the 30◦ targets, whereas the responses for acquiring the other targets had returned to baseline.

Eye and head amplitude Repeated-measures ANOVA indicated a significant effect of target position on the peak amplitudes of the eye saccade [F (2,360) = 864.8, P < 0.001] and head movement [F (2,360) = 1067,P < 0.001]). Spaceflight affected the peak amplitude of the head movement [F (3,360) = 4.38, P < 0.01], but not the peak amplitude of the eye saccade (Fig. 4C). Relative to preflight values, the head amplitude decreased on R + 0 by 1.5◦ -2.2◦ (P < 0.05) depending on the target offset (Fig. 4D). During both preflight and postflight tests, the gaze displacement remained essentially constant after the initial eye saccade ended (Fig. 2), indicating that the slow-phase eye compensation was very precise. During this phase of the response, the vestibulo-ocular reflex gain (ratio of eye velocity and head velocity) was near unity across all targets and test sessions. In addition, the number and amplitude of the corrective saccades at the end of the head movement toward the 60◦ targets were not significantly affected by spaceflight. Repeated-measures ANOVA indicated an effect of spaceflight on the final position of the eye in the orbit [F (3,360) = 3.16, P < 0.03] (Fig. 4E) and on the final position of the head in space [F (3,360) = 3.51, P < 0.02] (Fig. 4F). 7

Post-hoc tests revealed that the final eye position during acquisition of the 20◦ target was significantly larger on R + 0 (P < 0.01), R + 2 (P < 0.001), and R + 4 (P < 0.001) compared to preflight. This effect was also observed during acquisition of the 30◦ target on R + 2 (P < 0.01) and R + 4 (P < 0.01). The final head position during acquisition of the 20◦ target was significantly smaller than preflight on R + 0 (P < 0.001). This effect was also observed during acquisition of the 30◦ target on R + 0 (P < 0.001) and R + 2 (P < 0.001).

STEM Today, March 2019, No. 42

Effect of flight duration Figure 5A indicates that the increase in gaze latency immediately after landing (see Fig. 3) was not correlated with the duration of the flight. Each subject’s responses during visual target acquisition after spaceflight were normalized for each visual target according to their mean gaze latency before flight. Individual responses were then grouped by flight duration into 3 categories (short: 6-9 days; medium: 10-12 days; long: 13-17 days), and the group mean was calculated for each test session. The effects of spaceflight duration on the gaze latency were analyzed using repeated-measures ANOVA with 3 targets (20◦ , 30◦ , 60◦ ) X 3 durations (short, medium, long). There was no significant effect of target [F (2,360) = 0.23, P = 0.79] or spaceflight duration [F (2,360) = 1.41, P = 0.26] on gaze latency. Figure 5B illustrates mean gaze latencies for acquiring the 60◦ visual target (group average) after short, medium, and long-duration space missions.

The results of this study indicate that the time to acquire a visual target located 30◦ and 60◦ off center in the horizontal plane increased by 7-10% (30-34 ms) during the first few hours after return form space. This could potentially result in piloting errors because the astronauts will experience delays capturing operationally relevant targets during the critical period when they are returning to Earth. Time delays to acquire visual targets were consistent after short (6-9 days), medium (10-13 days), and long (14-17 days) duration Space Shuttle missions. Responses returned to normal 48 hours after landing. The increase in gaze latency was attributed to a decrease in velocity and amplitude of both the initial eye saccade and head movement toward the target.

Neurovestibular Symptoms in Astronauts Immediately after Space Shuttle and International Space Station Missions

Postural deficits and sensorimotor performance decrements have been observed in astronauts after they return 8

from short and long-duration missions. Results of these studies showed decrements in postural stability and increased time required for postural recovery, both of which intensified as a function of flight duration. However, previous investigations did not include testing during the first few hours after return from longduration missions onboard the International Space Station (ISS); the first post-flight testing was conducted 1 day after landing, when performance decrements had abated. Symptoms of vestibular disorders have been observed in astronauts immediately after return from short-duration missions onboard the Space Shuttle flights. These symptoms were recorded during medical debriefs between the astronauts and crew flight surgeons on the day of return (generally 2-4 hours after landing) and 3 days later. The severity of symptoms had considerably diminished 3 days after landing. Unfortunately, similar reports are not available for the immediate post-landing period of the Soyuz vehicle, which returns crewmembers from long-duration space missions on the ISS.

STEM Today, March 2019, No. 42

In this study, authors report symptoms of vestibular disorders and associated sensorimotor alterations measured in astronauts 1 to 5 hours after they return from short-duration Space Shuttle missions or long-duration ISS missions. The scientific objective of this study was to assess the effects of mission length on symptoms of vestibular disorders, especially instability of posture and gait. The operational objective was to determine whether the severity of the symptoms would impair the crews’ ability to quickly exit the vehicle in the event of an emergency.

The Space Shuttle crew members included 12 men and 2 women (mean ± SD age, 42.4 ± 5.0 years) who flew on 3 missions that lasted about 1 week (mean duration, 7.4 ± 0.9 days). Four crew members were participating in their first space mission, and the remaining 10 had flown on at least 1 other occasion. The ISS crew members included 16 men and 2 women (mean age, 45.5 ± 6.1 years) who were transported to and from the ISS on 8 Soyuz missions for missions that lasted about 6 months (mean duration, 175.8 ± 13.7 days). Seven crew members were participating in their first space missions, and 11 had flown on at least 1 other occasion. After a Space Shuttle mission, crew members were tested onboard the crew transport vehicle at the NASA Kennedy Space Center in Florida. This mobile clinic typically docked with the Space Shuttle within 20 minutes of landing. Astronauts left the Space Shuttle, with assistance if needed, via a short ramp to the crew transport vehicle, where they removed their reentry spacesuits and were examined and treated as necessary.

The time of exit from the Space Shuttle varied considerably but typically ranged from 30 to 45 minutes after landing. All subjects in the present study were examined within 1 to 2 hours after landing (mean duration, 1.2 ± 0.5 hours; Table 1). The crew members returned from long-duration ISS missions in the Soyuz capsule, which landed on the flat steppe of Kazakhstan in Central Asia. Testing was conducted in an inflatable tent at the Soyuz landing site or in a quiet room at the Karaganda airport (Kustanai) in Kazakhstan. Within minutes of landing, the astronauts were extracted from the capsule by the recovery teams. The crew members then sat in reclining seats before being moved to the inflatable tent for postlanding assessment. After all the medical checks were performed, crew members were then flown by helicopter to the Karaganda airport. Ten ISS crewmembers in the present study were examined in the tent 1 to 2 hours after landing, and 6 other ISS crewmembers were examined in the airport within 2 to 5 hours of landing (mean duration, 2.7 ± 1.6 hours; Table 1). Two crewmembers could not be tested in the tent or the airport because of severe motion sickness symptoms.

STEM Today, March 2019, No. 42

Results Vestibular and Motor Function Tests Table 3 shows the number of Space Shuttle and ISS subjects with positive results for each test. To compare the responses of the Space Shuttle and ISS subject groups, Fisher’s exact test was calculated for 2 X 2 contingency tables. Indeed, for comparing proportions between 2 populations, Fisher’s exact test tends to be more accurate than Pearson’s chi-square test when samples of 2 small populations are compared. The main observations are summarized as follows: • All Space Shuttle subjects had normal test results for saccade and pursuit tracking. • One Space Shuttle subject had an upbeating positional nystagmus when sitting upright that was detected through Frenzel goggles but considered to be within reference range. Attempts to induce paroxysmal positional nystagmus were negative for the 2 Space Shuttle subjects tested with the Dix- Hallpike maneuver. • Gaze-evoked nystagmus with prolonged gaze holding at large lateral and upward eccentricities was noted in 29% of Space Shuttle subjects and 38% of ISS subjects. • The most common abnormal finding was the incapacity to walk heel to toe along a straight line without stumbling or falling. This difficulty was demonstrated by 79% of Space Shuttle subjects and all 9 ISS subjects tested (100%). All subjects demonstrated abnormal broad-based gait during normal walking. The typical distance between the feet was 45 cm. • The next-most common abnormality, dysmetria during the pointing test, was exhibited by 71% of the Space Shuttle subject and 57% of the ISS subjects during their first few attempts at finger-tonose testing. All subjects achieved the target by the third to fifth attempts. • All subjects but 1 reported that standing immediately after landing required extraordinary effort. Fiftyseven percent of Space Shuttle subjects and 29% of ISS subjects could not stand from a seated position without assistance. Orthostatic intolerance, decrease in muscular strength, and microgravityinduced changes in central muscular coordination contributed to this deficiency. • Postural instability during the standing test was positive for 36% of the Space Shuttle subjects and 31% of the ISS subjects. The ISS crewmembers who were tested immediately after landing (ie, after the same delay as for the Space Shuttle crewmembers) did not have difficulties in maintaining upright balance. Subjective Reports All subjects reported feeling unstable or unbalanced when walking, particularly when making turns. Four Space Shuttle subjects had headaches after landing, and 3 subjects reported having had headaches during the first 2 or 3 days of flight. Post-flight headache in 1 of these individuals was related to position (worse when upright, relieved upon lying supine). Only 1 ISS crew member reported headache after landing. All 16 ISS subjects reported being nauseated immediately after landing. In addition to these 16 subjects, 2 other crew members could not be tested in the tent or at the airport because of severe reentry motion sickness symptoms. Interestingly, none of the Space Shuttle crew members had symptoms of reentry motion sickness after landing. However, 7 Space Shuttle subjects reported being nauseated, an indicator of space motion sickness, during the first few days of flight. Unfortunately, in-flight reports of 10

STEM Today, March 2019, No. 42

symptoms were not available for ISS crew members.

Fifty percent of Space Shuttle subjects and 75% of ISS subjects perceived motion of the environment or their body when they moved their head. Translational movements along the fore-aft, lateral, or vertical axis produced a sense of accentuated motion in that direction. One subject bent forward to counteract the sensation of falling in that direction and needed to straighten up abruptly to avoid falling. While Space Shuttle subjects stooped during postflight testing, they felt that the floor was "rushing up to meet them," a symptom that has been reported previously. This sensation ceased immediately when body or head motion stopped. Other symptoms described by Space Shuttle crew members included foot tingling when pressure was applied to the soles of the feet during reentry but not when walking after landing. Skin sensitivity changes have been reported in several other short-duration missions. Although ISS subjects did not report a tingling sensation in their feet, they all reported that their head and limbs felt very heavy after landing. None of the subjects reported diplopia, or double vision. Russian investigators previously reported that motion sickness during reentry affects 27% of the cosmonauts after short-duration missions (4-14 days) and 92% after longer duration missions (several months to 1 year). This results from the present study following ISS missions support these earlier reports.

The percentage of Space Shuttle subjects who had symptoms of vestibular disorders in the present study is similar to that reported for studies of 112 astronauts who flew on the Space Shuttle between 1996 and 2000. In these previous studies, the most frequent symptoms of vestibular disorders were persisting sensation aftereffects (60%), difficulty walking in a straight line (57%), unstable balance (48%), imprecise finger-to-nose pointing (20%), and use of arms for rising from a chair (14%). Post-flight sensory feedback, postural equilibrium, and motor performance have important implications for the success of potential emergency egress from the space vehicle immediately after landing. Space Shuttle and ISS subjects would both have serious difficulties egressing a spacecraft without assistance soon after landing in case of an emergency. A previous report estimated that 5% to 15% of Space Shuttle crew members would be unable to egress the Space Shuttle due to neurovestibular symptoms and orthostatic intolerance after landing. Since ISS crew members have a greater incidence of reentry-induced motion sickness, this might exacerbate performance of an emergency egress after long-duration missions.

STEM Today, March 2019, No. 42

Expedition 6

Due to the space shuttle Columbia accident, Expedition 6 was extended in duration to 5 1/2 months. The crew returned on a Soyuz spacecraft that landed in Kazakhstan. A spacecraft malfunction causing a ballistic entry displaced the landing site about 475 kilometers off course resulting in about a 5 hour delay for arrival of the ground support team. This gave the crew an opportunity to perform spacecraft safing, egress, and set up survival gear without any outside help.

Don Pettit explained his perspective in the paper "Mars Landing on Earth: An Astronautâ&#x20AC;&#x2122;s Perspective". Our Soyuz was TMA-1, the first flight vehicle off the production line in 25 years with a major upgrade to the cockpit. During entry, shortly after spacecraft separation from its propulsion and orbital modules, a small malfunction in a signal processing box that converts computer commands into jet firing signals caused us to loose the reaction control system (it is not known to the author if this malfunction was the result of the cockpit upgrade).

STEM Today, March 2019, No. 42

This malfunction occurred when we were out of radio contact with mission control. We downmoded to an unguided ballistic entry where we experienced over 8 g loadings and landed about 475 kilometers short of the nominal landing site. Following the initial landing impact, our capsule rolled a few times and ended up on its side about 30 meters from the point of touchdown. The trajectory brought us out of radio range for the parachute phase line-of-sight VHF radios, thus, the ground support team had no idea where we had landed. About two hours postlanding a search airplane flew overhead and we were able to make radio contact. About 3 hours after radio contact, the ground support personnel arrived via helicopter.

Due to these series of events, we as a crew performed a number of operational tasks previously not required by long duration crews. Given our sudden transitions from long term weightlessness, to 8 gâ&#x20AC;&#x2122;s, to the big thump, to being on our own in Kazakhstan, these tasks were physically taxing and not easy to accomplish. However, by working as a crew in this degraded state, we were able to take care of ourselves and complete basic survival tasks without outside help. We were not quivering sacks of Jell-O. This was due in part to the advancement in physiological countermeasures made on the International Space Station. While on our own we performed a number of basic operational tasks. We performed spacecraft safing. This involves reading procedures (in Russian), flipping switches, and pushing buttons on the control panel to power down unneeded equipment so that battery life for radio operations can be extended. Since the Soyuz capsule ended on its side, our operations were done from a position of being strapped into a seat fixed on a slanted ceiling. We opened the hatch, unstrapped, and crawled out. Following egress, we deployed the survival gear that was stowed in numerous small bundles throughout the spacecraft. Included were warm woolen cloths, food, water, a medical kit, a portable radio, and a signaling kit that contained a shotgun pistol that can fire flares as well as shotgun cartridges. Setting up a radio beacon was a priority.

We deployed two radio systems. One was a small VHF hand held radio that required assembly with its battery pack (transmitting power was 0.15 watt) and another that used the Soyuz VHF radio system with an external antenna. The antenna resembled a long, self-erecting tent pole and was bolted to a fixture on the hatch ring. There were no rescue aircraft within range. We unpacked food and water but no one was hungry. When the helicopters came near we fired a volley of flares from the shotgun pistol to signal our location. Performing these basic survival tasks was not easy. Moving was provocative. Your vestibular apparatus bitterly complained when there was head movement. Of the three of us, my symptoms were the greatest which is not uncommon for a rookie. Apparently, your body remembers the trials of past space flights making each additional one easier. For my crewmates, walking was labored but was done as needed shortly after landing. I had trouble walking but could crawl. By crawling back and forth between our Soyuz capsule and our mounting pile of survival gear I was able to contribute to our "base camp".

STEM Today, March 2019, No. 42

There were no systemic aches or pains associated with movement. We had good muscle strength. We had the lean muscled look of someone coming home from health camp, not the muscle-atrophied bodies from historic long duration space flight. My limbs felt heavy because my brain was not yet compensating for their weight. Like an electronic scale that tares out the weight of the beaker so that only the contents is weighed, your brain normally subtracts the weight of your limbs from the gravity equation so you primarily feel the weight that you hold. Upon returning, the brain had not yet kicked in this compensation which takes about 10 to 15 hours. Slow and deliberate motions were readily made with sufficient motor control to connect electrical wire harnesses, antennas, cycle switches on control panels, and shoot a shotgun pistol. Motor control for operating the spacecraft mechanisms and survival gear was not a problem. However, fast coordinated movement was not possible for me. We were able to accomplish the necessary operations by working as a team where we each contributed within our current physical ability. Perhaps most important, we were each able to take care of our personal needs; a down crewmember requiring care from a second person would have effectively reduced our crew of three to a crew of one.

Somatosensory Reweighting Following Spaceflight

Upright stance control depends on the continuous integration of vestibular, visual, and somatosensory afference, and any ambiguous or disrupted inputs from one of these sensory modalities may cause destabilization of standing balance. Previous studies have consistently reported an increase in body sway and impaired upright stance control in astronauts following prolonged exposure to microgravity. Misinterpretation of otolith signals (the otolith tilttranslation reinterpretation -OTTR-hypothesis), for example, has been proposed as possible mechanism of microgravityinduced maladaptive vestibular reorganization that degrade postural control and spatial orientation in astronauts while they are re-adapting to the return of gravitational inputs during early post-flight period . One compensatory strategy the CNS is capable of employing during this maladapted early post-flight period can be the dynamic update of relevant internal models through sensory reweighting. Sensory reweighting is an adaptive filtering process that regulates the relative contribution of each sensory modality to the internal model by down-weighting ambiguous afferences (e.g., vestibular) while up-weighting reliable sensory modalities to maximize overall gain and reduce signal-tonoise ratio. For example, if the surface conditions are firm and stable, somatosensory inputs from the feet mechanoreceptors and ankle proprioceptors are more reliable than when standing on a soft and compliant surface. Previous studies have shown that standard sensory organization tests (SOTs) may not be sensitive enough to detect subtle upright stance control dysfunctions in patients with vestibular disorders, who may compensate upright stance control performance by task vigilance during SOTs. Therefore, modified SOTs with dynamic head movements have been suggested for better fall risk diagnosis during functional postural control performance assessments, both in elderly and clinical populations. Furthermore, when vision is absent, introducing an additional experimental challenge to the vestibular system by dynamic 14

head movements would also allow us to better understand the compensatory role of sensory reweighting as a function of the availability of reliable somatosensory inputs.

STEM Today, March 2019, No. 42

Therefore, authors hypothesized that: availability of reliable somatosensory cues, in the absence of vision, will mitigate destabilizing effects of both impaired (due to microgravity) and distorted (due to head tilts) vestibular function during upright stance control. As a secondary purpose, they compared postural control performance from pre-flight and return day sessions’ of astronauts with healthy elderly individuals to better understand aging-related sensorimotor aspects of increased body sway.

Postural control performance during disturbed vestibular function and compromised somatosensory inputs was systematically monitored in 11 astronauts (7 males, 4 females; age range 38-49 years) before and after shortduration (11-13 days) Shuttle flights, and 11 matched controls who followed the same time line as astronauts but did not fly into space. Postural control performance of astronauts before and immediately after returning from spaceflight was also compared with nine healthy elderly subjects (3 males, 6 females; age range 73-86 years) to infer sensory mechanisms underlying postural control impairments in the elderly population. Each astronaut subject was a first-time flier. Each control subject was matched with an astronaut subject in terms of age (±4 years), sex, height (±5 cm), weight (±5 kg), and postural control performance [same quartile of Composite Equilibrium Score (EQ)]. Time spacing between pre- and post- "flight" sessions for controls was the same as that of matched astronauts. Postural control performance was assessed using computerized dynamic posturography (CDP). All subjects were participating in the CDP testing for the first time; hence any learning effects should have been similar 15

STEM Today, March 2019, No. 42

for all groups. All astronauts passed NASA spaceflight physical examination prior to their missions, and control subjects had passed an Air Force Class III physical examination within 12 months of beginning the study. None of the astronaut or control subjects reported any history of balance or vestibular abnormalities.

Elderly subjects were selected among those with no known neurological, cardiovascular, vestibular or musculoskeletal disorders, and no history of falls for at least 6 months before the start of the study. Overall health status of elderly subjects was screened by using the Physical Activity Readiness Questionnaire PAR-Q. To establish pre-flight postural stability baseline data, each astronaut subject participated in four pre-flight testing sessions at JSC, occurring 141 (± 35), 133 (± 35), 50 (± 7), and 14 (± 1) days before launch (mean ± standard error of mean (SEM)), designated as familiarization (FAM), L-60, L-30, and L-10 sessions, respectively (Figure 1). The first pre-flight session,which occurred at least two days before the second pre-flight session, was considered FAM training for the postural tests using the standard SOTs, and data from this session were excluded from the analyses. The other three pre-flight sessions were considered to be independent estimates of a putatively stable individual. While nominally scheduled for 60, 30, and 10 days before the flight, launch schedules often

shifted after one or more sessions had been completed. Since authors did not have any reason to believe that the usual performance of astronauts would have been affected by launch delays, they accepted the actual timing while still classifying them based on expected timing. The first post-flight session (R+0) was performed at the Kennedy Space Center (KSC), Florida within 2-5 h after return from spaceflight using an experimental setup identical to that at JSC. All subsequent post-flight sessions were performed at JSC at 2 (R+2), 3 (R+3) and 7 or 8 (R+7/8) days after return from spaceflight. The second (L-60) and third (L-30) pre-flight sessions, and the third (R+3) postflight session included the experimental postural tasks before and after exposure to shortradius centrifugation. However, only pre-centrifugation data are presented here. Astronaut and control subjects were instructed to avoid exposure to other unusual motion environments, strenuous physical activities or other experiments that might disrupt their recovery of balance function. Elderly subjects participated in a single session which included both familiarization and testing trials.

STEM Today, March 2019, No. 42

Results Figure 2 illustrates the time series data during different postural control performance conditions from a representative astronaut subject and an elderly subject. Learning Effects in Control Subjects For the SOT-2 HE condition (Figure 3. blue triangles), there was a significant improvement (i.e., lower iTTB) at R+0 in comparison to L-60 (Z = 2.134, p = 0.033). However, no change was observed from R+0 to R+7/8 sessions (p > 0.05), indicating that postural control was fine-tuned from L-60 to R+0 sessions and was stabilized after R+0. For the SOT-2 HD condition, postural control performance was stable across sessions. During SOT-5, significant learning effect was observed between L-60 and L-10 in the HE condition [t(8) = 3.161, p = 0.013], and then the performance remained stable for the following sessions. For the HD condition during SOT-5, there was a decreasing trend. However it was not significant (p > 0.05), and thus authors can conclude that the postural control performance was stable across sessions. Postural Control Performance Before and After Spaceflight Results of the independent sample t-tests showed no significant (p > 0.05) difference in postural control performance between control and astronaut subjects during any of the pre-flight sessions (L-60, L-30, and L-10) for either head condition (HE,HD) or support surface condition (SOT-2, SOT-5). Nor were any learning effects observed for astronaut subjects during pre-flight sessions for either head condition or support surface condition (p > 0.05). To understand the effects of spaceflight on postural control, a series of paired comparisons were carried out between postflight and pre-flight sessionsâ&#x20AC;&#x2122; in astronaut subjects. Since no learning effect was observed in astronaut subjects pre-flight, data of L-60 was used to compare with the data of the post-flight sessions of astronauts. For SOT-2, postural control performance was significantly reduced, i.e., higher iTTB, in the R+0 session when compared to the pre-flight session [R+0 vs. L-60 - HE: t(10) = 3.020, p = 0.013; HD: t(9) = 3.763, p = 0.004] for both head conditions (Figure 3, red triangles). For the HE condition in SOT-2, postural control performance became similar to the pre-flight level at the R+2 (R+2 vs. L-60: p > 0.05) session and remained stable during the following two post-flight sessions (p > 0.05 for R+2 vs. R+3, and R+3 vs. R+7/8). For the HD head condition in SOT-2, postural control performance returned to the pre-flight level only at the R+7/8 [RC2 vs.L-60: t(9) = 3.540, p = 0.006; R+3 vs. L-60: t(10) = 3.370,p = 0.007; R+7/8 vs. L-60: p > 0.05] session indicating a slower recovery in postural control performance during HD trials. For SOT-5 trials, postural control performance significantly deteriorated in R+0 session when compared to the pre-flight session [R+0 vs. L-60 - HE: Z = 2.073, p = 0.038; HD:t(9) = 6.539, p < 0.001] for both head conditions (Figure 3,red circles). Pairwise comparisons showed that in the HE condition, postural control performance returned to the pre-flight level at the R+2 session (R+2 vs. L-60: p > 0.05) and remained stable during the following sessions (p > 0.05 for R+2 vs. R+3, and R+3 vs. R+7/8). In the HD head condition, however, postural control performance was still impaired at the R+2 session compared to the pre-flight sessions (R+2 vs. L-60: Z = 2.803, p = 0.005) and returned to the pre-flight level only at the R+3 session and remained stable after that (p > 0.05 for R+3 vs. L-60, and R+3 vs. R+7/8), indicating longer recovery time when vestibular system was challenged. The Role of Somatosensory Inputs For both astronaut and control subjects, authors used data from the R+0 session to examine whether the 17

STEM Today, March 2019, No. 42

availability of reliable somatosensory information could compensate for dynamic head tilt related performance decrements in balance control especially when the vestibular system is in a maladapted state due to microgravity effects on vestibular functioning.

First of all, authors compared SI between the SOT-2 and SOT-5 conditions in control subjects (Figure 4B)and found that the SI for SOT-2 was significantly higher than the SI for SOT-5 (Z = 2.756, p = 0.006). This confirms, as expected, the importance of a stable, veridical, Earth-fixed reference for somatosensory inputs in HD compared to HE. Next, they compared the effects of spaceflight on the SI for SOT-2 (Figure 4C) and found that the SI was significantly lower in astronauts on the return day than in controls [t(19) = 2.404, p = 0.027]. While this might suggest a reduction in reliance on somatosensory cues, it seems more likely that there could be some inaccuracies in somatosensory processing associated with spaceflight or that the alterations in the vestibular system associated with spaceflight were too profound to be fully compensated for by the somatosensory system. Furthermore, they compared the effects of spaceflight on SRwI (Figure 4D) and found SRwI to be nearly an order of magnitude higher in astronaut subjects on the return day than in control subjects (Z = 2.746, p = 0.005). This suggests a much higher reliance on somatosensory cues after spaceflight, even when they are inaccurate, confirming our primary hypothesis. Authors then compared VI in control subjects between the two head conditions (Figure 4E) and found that the VI of HE was significantly higher than that for HD (Z = 2.756, p = 0.006). This confirms that, as expected, reliance on vestibular input decreases with HD. As expected, VI during HD for astronaut subjects on the return 18

STEM Today, March 2019, No. 42

day was significantly lower than that in controls (Figure 4F, Z = 3.380, p < 0.001), clearly demonstrating a decreased reliance on vestibular inputs early after spaceflight.

Finally, authors assessed relative decrements in performance after spaceflight associated with the vestibular and somatosensory systems by comparing SCI and VCI on the return day (Figure 4G). They found that the VCI was significantly lower than the SCI (Z = 2.803, p = 0.005), suggesting that the relative decrement in reliance on vestibular inputs was far greater than that for somatosensory inputs, resulting in a relative increase in reliance on somatosensory inputs. Another functional performance metric is the number of fall (loss-of-balance) incidences observed under each test condition (Table 1). None of the subjects lost balance on any trial of SOT-2. The only two fall incidences observed in control subjects occurred during SOT-5 trials with HD (Table 1; bottom row). Conversely, on return day, all 11 astronaut subjects fell on at least one of two HD trials during SOT- 5, and three astronaut subjects fell on one of the two HE trials during SOT-5. By R+2, recovery was well underway, as the incidence of falls on SOT-5 trials with HD decreased to 5/22, and beyond that, recovery was essentially complete, with only one fall observed in each of the final two test sessions. Astronaut vs. Elderly Comparisons To gain better insights regarding postural control impairments in the elderly subjects, authors compared postural control performance of elderly subjects during SOT-2 and SOT-5 trials (only HE) with the astronaut subjects pre-flight (L-60) and immediately after return (R+0), in both head conditions (Figure 5). Pre-flight comparisons showed that postural sway was significantly higher in elderly subjects when compared to the HE [SOT-2: t(18) = -3.437, p = 0.007, SOT-5: t(17) = -5.810, p < 0.001], and the HD [SOT-2:t(18) = -2.347, p = 0.031, SOT-5: t(18) = -2.279, p = 0.035] conditions in astronaut subjects. The R+0 performance comparisons for SOT-2 trials showed no significant difference in performance between the HD condition in astronaut subjects and the HE condition in elderly subjects (p > 0.05), while in the HE condition in astronauts, postural sway was still significantly lower than that of elderly subjects in the HE condition [t(18) = -2.370, p = 0.029]. For SOT-5 trials on R+0, however, astronaut performance in the HD condition was significantly worse [t(17) = 5.190, p < 0.001] than that of elderly subjects in the HE condition, and no significant differences were found in HE trials between astronauts and elderly subjects (p > 0.05). Overall comparisons show that astronauts on R+0 (i.e., with a maladapted vestibular system) perform better than elderly subjects only when somatosensory 19

cues are reliable.

STEM Today, March 2019, No. 42

The results also show that astronauts on the return day perform comparable to the elderly when vestibular inputs are disrupted through HD or when somatosensory cues are compromised, and perform worse than the elderly when vestibular inputs are disrupted through HD in compromised somatosensory condition.

Consistent with previous studies, astronautsâ&#x20AC;&#x2122; postural control performance was significantly degraded on the return day (R+0), in all postural control tasks and head conditions. Although somatosensory contributions to postural control may also have been degraded in astronauts, short-duration spaceflight primarily impaired vestibular functioning such that vestibularly deficient astronauts were able to maintain their upright stance when somatosensory cues were relatively reliable on a stable surface but inevitably fell when a sway-referenced surface further challenged the reliability of somatosensory cues in the absence of vision. Considering the incidence of falls during sway-referenced postural tasks, the analyses demonstrated the critical role of reliable somatosensory cues on functional upright postural control when the vestibular system is maladapted during the early post-flight period. Finally, comparable postural control performance between elderly and vestibularly deficient astronauts during challenging vestibular conditions on the return day supports current aging literature and suggests that therapeutic strategies enhancing sensorimotor integration can improve postural control performance in older adults. Somatosensory Functioning Is Less Affected by Spaceflight and Critical During Maladapted Vestibular Functioning in Astronauts The analysis on the sensory ratios showed that the destabilizing effects of dynamic head movements on upright stance control change, as a function of reliable somatosensory inputs with respect to the surface-vertical, considerably in healthy controls but critically in vestibularly deficient astronauts. Specifically, when control subjects performed dynamic head movements blindfolded on a fixed support surface

(SOT-2), providing reliable somatosensory inputs regarding body orientation, SI index was very high (0.95 Âą 0.05) indicating that the performance difference between HE and HD is negligible in SOT-2 (Figure 4B red bar). However, when the dynamic head movements were performed on a sway-referenced support surface (SOT-5), compromising the reliability of somatosensory inputs, SI index was significantly lower (0.76 Âą 0.06), suggesting a notably destabilizing effect of HD on upright stance performance even in healthy controls for SOT-5 trials (Figure 4B blue bar). Additionally, authors also recorded two fall incidences during SOT-5 HD condition, and no fall during SOT-5 HE condition (Table 1), suggesting that the availability of reliable somatosensory cues may compensate for disrupted vestibular inputs in healthy controls.

STEM Today, March 2019, No. 42

However, this somatosensory driven compensation may become critical in vestibularly deficient astronauts immediately after spaceflight. Although authors observed decreased SI and VI indices (Figures 4C,F) in astronauts, suggesting both impaired somatosensory and vestibular functioning, the degree of impairment was substantially higher in vestibular functioning following spaceflight. By comparing the ratio of changes in SI and VI between astronauts and healthy controls (Figure 4G), authors showed a relatively high SCI but substantially decreased VCI, meaning astronauts were almost as good as healthy controls to utilize reliable somatosensory but were unable to use vestibular cues for compensating the destabilizing effects of HD. This suggests that somatosensory inputs are still relatively reliable sensory feedback source for vestibularly deficient astronauts, and thus they rely more on the less affected sensory system (somatosensory cues) to monitor their standing balance in the absence of vision while the CNS resolve transient vestibular deficiencies immediately upon return. Authors further supported these findings by showing an increased reliance into somatosensory weights in vestibularly deficient astronauts immediately after spaceflight (Figure 4D). In fact, availability of relatively reliable somatosensory cues was crucial for astronauts such that 20 out of 22 trials (% 90.9) resulted in falls when the validity of somatosensory cues for referencing gravitational vertical is further challenged during SOT-5. On the other hand, no single fall was observed when somatosensory cues could be used to infer gravitational vertical during SOT-2 trials. Thus the primary finding of this study is the critically functional role of somatosensory inputs from foot sole cutaneous receptors and ankle joint proprioceptors for maintaining upright stance in vestibularly deficient astronauts following spaceflight. Considering all the analyses authors performed along with fall incidences, the difference between falling and standing for an astronaut during maladapted vestibular functioning seems to heavily depend on the reliability of somatosensory cues monitoring body sway with respect to the gravitationalvertical.

Decreased otolith-mediated vestibular response in 25 astronauts induced by longduration spaceflight

To coordinate movements, ensure balance, and maintain stable gaze, humans depend on the peripheral vestibular labyrinth, located bilaterally in the inner ear. The vestibular system senses head movements and provides the brain with the necessary information about our spatial orientation. The vestibular system consists of two main parts: the semicircular canals, which sense rotational movements, and the otolith organs detecting the sum of linear accelerations acting on the head. The sum is referred to as the gravito-inertial acceleration (GIA) vector (see Fig. 1). Otolith-driven eye movements reflect the response of the sensory epithelia to both translation and tilt (with respect to gravity) of the head. One example of an otolith-driven response is ocular counterrolling (OCR), which is generated when we turn around a corner (walking, driving, or biking) or undergo centrifugation. The OCR tends to orient the eyes toward the GIA. The ability to complete the orientation is thought to be crucial for the postural stability during movements.

STEM Today, March 2019, No. 42

The importance of the vestibular system, as well as the importance of gravity, for our ability to maintain balance becomes particularly clear when studied in relation to spaceflight. When orbiting around Earth, the space crew inside the International Space Station (ISS) is in a so-called "free fall," meaning that instead of the 1-g gravity environment humans experience on Earth, the gravity is reduced to 10â&#x2C6;&#x2019;6 g, i.e., microgravity. The vestibular receptors (the utricle and saccule) are the primary gravity sensors of the body, and their gravity dependence makes them especially vulnerable in a microgravity environment. In the absence of gravitational inputs, the otoliths will be forced to adapt to the new condition to be able to orient in space. During the adaptation process, a deconditioning (decrease in gain of otolith-mediated reflex) of the otolith system is thought to take place, which is hypothesized to be the cause of several of the symptoms reported in returning astronauts, such as balance problems and dizziness. When the astronauts reenter the gravitational environment on Earth, a majority of them experience, among other effects, orthostatic intolerance and spatial disorientation as well as gaze control problems. Several studies have shown an activation of sympathetic outflow in response to postural changes, and therefore the otolith system is also hypothesized to be important in the prevention of orthostatic intolerance. A recent study has added evidence for the link between the vestibular and autonomic systems. Since OCR is an accepted way to evaluate the condition of the otolith system, a number of studies have used the OCR as a measurement of the effect of microgravity on the vestibular system. However, there are contradicting results from studies showing an increase, a decrease, or no change in OCR on return compared with before flight. Clement and colleagues wrote a review covering all OCR data induced by static whole body tilt after (short term) shuttle missions in 2007. The 18 astronauts showed no significant change in OCR after flight compared with before flight (Clement et al. 2007). An important limitation of the studies evaluating centrifuge-induced OCR so far is the fact that all researchers investigated a small sample size, mostly because of the overall difficulty and restrictions on astronaut access.

In addition, the above-mentioned results mostly come from short-term spaceflight, which makes it difficult to generalize to the effect of long-term exposure to microgravity. More recently, a couple of studies focusing on OCR induced by head tilt, the so-called static torsional otolith-cervical-ocular reflex (OCOR), have been performed by Kornilova and colleagues. They concluded that the otolith function was suppressed early after spaceflight and that it recovered within 8 or 9 days. The aim of this study was to investigate whether long-term exposure to microgravity results in changes in the otolith-mediated response OCR in returning astronauts. As hypothesized, a possible otolith deconditioning could be responsible for a number of negative effects seen in returning astronauts.

STEM Today, March 2019, No. 42

Authors measured the otolith-mediated OCR response induced by centrifugation in a space crew before and after spaceflight to evaluate the otolith-mediated vestibular reflex. They conducted the experiments in the Gagarin Cosmonaut Training Centre (Star City) near Moscow, Russia. A group of 25 (24 men and 1 woman) cosmonauts (average age of 46 yr, SD ± 6 yr) from the Russian Space Agency (Roscosmos) and 1 from the European Space Agency (ESA) (all denoted here as astronauts) took part in the study. The astronauts were tested before and after a 6-mo stay in the ISS. The average number of days spent in space was 164 (SD ± 22). The first astronaut participating in the study was tested in 2007 (ISS expedition 16) and the last one in 2015 (expedition 43). The pre-flight data were based on two baseline experiments [baseline data collections (BDCs)] that were conducted on average 55 (SD ± 29) days before launch. The astronauts were tested again two or three times after flight. The first post-flight experiment took place 2 or 3 days after return (R+2/3), the second one 4 or 5 days after return (R+4/5), and the last one 9 or 10 days after return (R+9/10). Because of medical and organizational issues, we were not able to test all of the astronauts on the same day after return. On average, the first measurement took place 3.6 days (SD ± 1.2 days) after return to Earth For the experiment, the subject was seated in the Visual and Vestibular Investigation System (VVIS), a small centrifuge (rotation chair; see Fig. 1) built for the Neurolab shuttle mission. The astronaut was securely fixed in the chair, and head movements were restricted. The entire room was darkened to avoid visual motion feedback during rotation. The centrifuge allowed earth vertical rotation on a fixed distance of 0.5 m from the axis of rotation. In front of the astronaut, a screen was placed on which visual targets were present during parts of the experiments. After calibration of the video-goggles and a baseline recording, the astronaut was subjected to 1 g for 5 min in a counterclockwise (CCW) direction and 5 min in a clockwise (CW) direction subsequently. The rotation was always performed first in CCW and then in CW direction with a short pause in between (when the chair was turned around). The subject was facing the direction of motion for both CCW and CW rotation, right ear out during CCW rotation and left ear out during CW rotation. The maximum velocity of 254◦ /s was chosen to obtain a centripetal acceleration of 1 g outward. Combined with gravity, such a shear force constitutes a virtual sideways tilt of 45◦ (θ = 45◦ in Fig.1), inducing an OCR of typically 5-7◦ , given a OCR gain of ≈15% in normal conditions.

STEM Today, March 2019, No. 42

Results Differences in OCR at different time points To model the change in OCR following a spaceflight, a linear mixed model of OCR vs. time was fitted, as described in METHODS, with time including all four time points [BDC, R+2/3, R+4/5, last experiment after flight (R+9/10)].

Not all astronauts were available for testing three times after flight, because of the evident restrictions in astronaut schedule and access. Therefore, the first postflight measurement was either 2 or 3 days (1 astronaut was tested on R+1) or 4 or 5 days after reentry. The linear mixed model showed a highly significant effect of time on the OCR (P<0.001). A post hoc analysis, comparing preflight OCR with OCR at the three post-flight time points, showed a statistically significant decrease in OCR at R+2/3 and at R+4/5. At R+9/10, there was no longer a difference in OCR compared with preflight OCR values. In Table 1, the OCR values, including standard deviation and standard error, can be found.

Of the 25 subjects, 19 had a decreased OCR after flight, 3 had no change or a very small change, and 1 had an increase in OCR after spaceflight. Two of the 25 subjects were not available for testing R+2/3 or at R+4/5, because of complications. For those two, authors only have pre-flight data and OCR data from R+9/10. For comparison purpose, they also report the gain (Table 1). This was computed by dividing all OCR values by 45◦ , the tilt of the GIA.

Figure 3 shows the mean values of OCR (including standard error) for the four time points, averaged over directions and eyes; the figure displays the OCR for the preflight experiment (6.99 ± 0.66◦ ) as well as for the three postflight experiments. Figure 4 shows the average raw OCR data response grouped according to the direction of rotation; in each diagram, i.e., for each rotation, the recorded OCR of the two eyes is also individually presented. Differences in OCR between two directions of rotations During the centrifugation, the subject was always rotated first CCW and then in the CW direction, with a short pause in between. When comparing the OCR data from the two directions of rotations for the pre-flight experiment, using the linear mixed model, authors observed a significantly higher OCR for the CCW (first direction of) rotation. The recorded OCR value was 0.57◦ (SE= 0.22◦ , P = 0.008) lower during CW rotation compared with that recorded during CCW rotation. For the post-flight experiments, no significant difference between the rotation directions was found. First-time fliers vs. experienced fliers. Of the 25 astronauts, 13 were first-time fliers and 12 had been flying at least once prior to our study, with 2 of them already flying four times before participating in our experiment. Authors compared OCR vs flight experience for the two groups, using the linear mixedmodel. Authors saw a trend in the difference in OCR between the two groups. The OCR was consistently lower, across all time points, for the group of experienced fliers compared with the first-time fliers, but at none of the time points was this difference significant. A model across all time points gave an OCR that was on average 0.99◦ lower (SE = 0.68◦ ) for the experienced fliers (P > 0.05). 24

The OCR response was significantly decreased early after spaceflight (at R+2/3 and R+4/5). This indicates that the otolith-mediated vestibular response among the astronauts was affected during the first days after return, likely because of the absence of gravitational input during the preceding 6 mo. A recording of a lower OCR after spaceflight agrees with a number of studies performed in the last decades . Clement and colleagues found no significant change in OCR after flight compared with before flight in 18 astronauts tested after (short term) shuttle missions (Clement et al. 2007). A possible reason for this could be the duration of the shuttle missions, < 2 wk, while the data collected in the present study cover astronauts who spend 6 mo in space. Another difference, however, may be due to the difference in vestibular stimulation between static tilt (which elicits response from the vertical semicircular canals) and centrifugation (which does not). An important limitation of the studies evaluating centrifuge-induced OCR so far is the fact that all investigated a small sample size, which has made generalization difficult.

STEM Today, March 2019, No. 42

The strong significance of the decreased OCR adds to the evidence that microgravity causes adaptive changes in the otolith-mediated vestibular response. At the last postflight experiment, 9 days after return, there was no longer a significant difference of the measured OCR response compared with pre-flight values. This suggests that the OCR reflex was back at baseline level and that the otolith-mediated system was fully recovered, which agrees with the results of Kornilova et al. (2012). This delay in adaptation of the otolith-mediated vestibular response can have negative consequences for astronauts when reentering gravity. In this study, authors were not able to correlate the change in OCR with any of those parameters associated with disequilibrium. Entering a gravitational environment other than the one here on Earth, such as for example Martian gravity, while not being able to fully function during the first days after landing may have severe consequences for the crew. There will be no room for mistakes during a recovery period. Preferably, it would not be necessary to recover if the cause (lack of gravity) could be removed in the first place. The present data suggest a recovery rate of a little over 1 wk, but this reflects the vestibular response. A recent single case study, however, has shown that even 9 days after return an astronaut still showed alterations in the cortical vestibular network, as measured by means of functional MRI. This suggests that the underlying neural adaptation takes longer than is seen in the vestibular reflex based on peripheral end organs, e.g., the otoliths. Evidently, this must be investigated further in a larger sample size, but the question arises of where the impact of microgravity takes place, i.e., on the peripheral end organ at the level of the otoliths or more centrally. The OCR response was found to be higher during the CCW (first rotation) than for the recording during the CW rotation, which could be a consequence of habituation. During postflight experiments, the difference was no longer significant between the two tests (CCW and CW). It could be speculated that a difference in OCR between the two rotations was still present, but because of the lower postflight OCR values the difference was too small to detect. Up front, authors did not expect to find a difference in OCR between the two directions. To their knowledge, this has not been seen in previous studies. To make any conclusion concerning a learning effect, further testing would be necessary, preferably with a counterbalanced order of the two directions of rotation. Even though the mean OCR was consistently lower across all time points for the group of experienced fliers, for none of the time points was this difference significant. Within both groups the variance in OCR was large, so even if a lower OCR was observed the P value was not significant. Moreover, the large variance is likely due to the fact that the experienced fliersâ&#x20AC;&#x2122; group was a heterogeneous mixture of second-, third-, and fourth-time fliers. Preferably, the same subject should be measured at least twice, first as a first-time flier and then again as an experienced flier. From a study design point of view, pairwise tests within subjects are a much stronger and more powerful analysis, as each subject acts as his/her own control. Therefore, authors cannot exclude that flight experience can have a significant influence on the OCR response. A test-retest study with the same subjects is currently ongoing to further investigate this phenomenon.

STEM Today, March 2019, No. 42

References R

Reschke, Millard F et al."Eye-Head Coordination in 31 Space Shuttle Astronauts during Visual Target Acquisition" Scientific reports vol. 7,1 14283. 27 Oct. 2017

Reschke MF, Good EF, Clement GR. Neurovestibular Symptoms in Astronauts Immediately after Space Shuttle and International Space Station Missions. OTO Open. 2017 Oct 23;1(4)

Gorgiladze GI, Bryanov II. Space motion sickness. Kosm Biol Aviakosm Med. 1989;23:4-14.

Clark JB, Bacal K. Neurologic concerns. In: Barratt MR, Pool SL, eds. Principles of Clinical Medicine for Space Flight. New York, NY: Springer; 2008:361-379.

Bloomberg JJ, Mulavara AP. Changes in walking strategies after space flight. IEEE Eng Med Biol Mag. 2013;22:58-62.

Wood SJ, Loehr JA, Guilliams M. Sensorimotor reconditioning during and after spaceflight. NeuroRehabilitation. 2011;29:185-195.

Wood SJ, Paloski WH, Clark JB. Assessing sensorimotor function following ISS with computerized dynamic posturography. Aerosp Med Hum Perform. 2015;86(suppl 12):A45-A53.

Pettit D. Mars landing on Earth: an astronautâ&#x20AC;&#x2122;s perspective. J Cosmology. 2010;12:3529-3536.

Ozdemir RA, Goel R, Reschke MF, Wood SJ, Paloski WH. Critical Role of Somatosensation in Postural Control Following Spaceflight: Vestibularly Deficient Astronauts Are Not Able to Maintain Upright Stance During Compromised Somatosensation. Front Physiol. 2018;9:1680. Published 2018 Nov 27.

Hallgren E, Kornilova L, Fransen E, Glukhikh D, Moore ST, Clement G, Van Ombergen A, MacDougall H, Naumov I, Wuyts FL. Decreased otolith-mediated vestibular response in 25 astronauts induced by longduration spaceflight. J Neurophysiol. 2016 Jun 1;115(6):3045-51.

Clement G, Denise P, Reschke MF, Wood SJ. Human ocular counter-rolling and roll tilt perception during off-vertical axis rotation after spaceflight. J Vestib Res 17: 209-215, 2007.

Kornilova LN, Temnikova VV, Sagalovich SV, Aleksandrov VV, Iakushev AG. Effect of otoliths upon function of the semicircular canals after long-term stay under conditions of microgravitation. Ross Fiziol Zh I M Sechenova 93: 128-140, 2007a.

Kornilova LN, Naumov IA, Azarov KA, Sagalovitch VN. Gaze control and vestibular-cervical-ocular responses after prolonged exposure to microgravity. Aviat Space Environ Med 83: 1123-1134, 2012.

Kornilova LN, Naumov IA, Makarova SM. Static torsional otolith-cervicalocular reflex after prolonged exposure to weightlessness and a 7-day immersion. Acta Astronaut 68: 1462-1468, 2011.