Long-duration spaceflight adversely affects post-landing operator proficiency

Performance of astronaut pilots during space shuttle landing was degraded after a few weeks of microgravity exposure, and longer-term exposure has the potential to impact operator proficiency during critical landing and post-landing operations for exploration-class missions. Full-motion simulations of operationally-relevant tasks were utilized to assess the impact of long-duration spaceflight on operator proficiency in a group of 8 astronauts assigned to the International Space Station, as well as a battery of cognitive/sensorimotor tests to determine the underlying cause of any post-flight performance decrements. A ground control group (N = 12) and a sleep restriction cohort (N = 9) were also tested to control for non-spaceflight factors such as lack of practice between pre- and post-flight testing and fatigue. On the day of return after 6 months aboard the space station, astronauts exhibited significant deficits in manual dexterity, dual-tasking and motion perception, and a striking degradation in the ability to operate a vehicle. These deficits were not primarily due to fatigue; performance on the same tasks was unaffected after a 30-h period of sleep restriction. Astronauts experienced a general post-flight malaise in motor function and motion perception, and a lack of cognitive reserve apparent only when faced with dual tasks, which had recovered to baseline by four days after landing.

For future exploration-class missions to asteroids or other planetary bodies crewmembers will be required to perform operational tasks following extended periods of microgravity exposure. It is well documented that astronauts returning from long-duration missions to the International Space Station (ISS) exhibit adverse sensorimotor 1 , cardiovascular 2 and neuromuscular 3 effects upon return to Earth due to in-flight adaptation to microgravity. How these physiological changes affect post-landing operator proficiency is not well understood, but results from the shuttle era demonstrate that even short-duration missions adversely affect pilot performance. Our analysis of touchdown speeds for the first 100 missions 4 demonstrated that 20% of orbiter landings were outside of acceptable limits, and the maximum speed of 217 kts (main gear tire limit) had been equaled or exceeded six times. The hardest touchdown on record (STS-90 at 224 kts) occurred following the commander's momentary loss of orientation ('tumbling the gyros') after an active head movement just prior to touchdown 4 , and the second hardest touchdown (STS-3 at 220 kts) involved a pilot-induced oscillation after main-gear touchdown and prior to derotation (nose-gear touchdown) 4 .
Although no piloted landings have occurred following long-duration missions, the collision of the unmanned Progress 234 with the Mir space station in 1997 suggests that prolonged spaceflight can negatively impact operator performance. In this instance the commander, after 136 days on orbit, was tasked to remotely pilot the Progress from a distance of 6 km to dock with Mir. The collision was initially attributed to piloting errors in the form of 'late realization that the closing rate was too high' and 'incorrect final avoidance maneuvering' 5 , although subsequent reviews determined that a variety of other factors contributed to the accident, such as fatigue (the commander's request to withdraw from a sleep study due to chronic lack of sleep was refused by mission control prior to the collision) 6 , issues with the range radar (it was turned off for the final docking attempt at the behest of mission control), and inadequate planning and crew training 7 .There have been five significant teleoperation www.nature.com/scientificreports www.nature.com/scientificreports/ Services 45 CFR 46. Subjects gave their written informed consent and were free to withdraw at any time. All test sessions were conducted in Building 266 at NASA Johnson Space Center (JSC), Houston, Texas.
The astronaut subjects were tested four times pre-flight and three times post-flight. The first 90-minute session, scheduled on average 167.5 days (SD 62.6) prior to launch, was used to familiarize crewmembers with the cognitive/sensorimotor test battery and the driving simulations (data from these sessions were not analyzed). Baseline data were obtained from the subsequent three 60-min pre-flight sessions, which occurred 129.8 (SD 15.2), 82.1 (SD 10.5) and 73.8 (SD 10.0) days before launch. Crewmembers were tested at JSC on the day of return from the ISS (R + 0) approximately 20-22 h after touchdown in Kazakhstan, corresponding to late evening (10:00 pm -midnight) Houston time, following a 'direct return' from Karaganda aboard a NASA Gulfstream III aircraft. Due to mission constraints one subject was not available for testing until 7:00am Houston time the day after landing (approximately 30 h after touchdown). The mean gap between the final pre-flight test and the first post-flight session was 244.6 days (SD 14.5; range 217-267). The second and third post-flight sessions were conducted 4.1 days (SD 0.8; range 3-5) and 8.1 days (SD 1.2; range 6-10) after return (labelled R + 4 and R + 8, respectively).
Shadow testing was scheduled to closely mirror that of the astronaut subjects. Four baseline sessions (a 90-min familiarization followed by three 60-min baseline data collection sessions, analogous to the astronaut pre-flight schedule) were conducted with an average interval between sessions of 8.8 days (SD 1.1; range 7-12). The mean gap between the final baseline and first 'post-gap' session (G + 0, analogous to R + 0) was 244.8 days (SD 7.6; range 236-257), which was almost identical to the mean interval between the final pre-flight and first post-flight session for the astronauts (244.6 days). The second (G + 4) and third (G + 8) post-gap sessions were held 3.5 (SD 0.8; range 3-5) and 7.3 (SD 0.8; range 6-8) days after the G + 0 session.
Subjects participating in the sleep restriction group performed three 60-min baseline sessions (analogous to astronaut pre-flight testing) an average of 6.1 days (SD 2.4; range 4-10) apart; the first session was a combination familiarization/data collection session, the final two were data collection only. A week after the third baseline session (7.1 days SD 0.3; range 7-8) subjects participated in a 'post-sleep deprivation' session (S + 0, analogous to R + 0), following a 30-h sleep restriction protocol (see below).
Cognitive/sensorimotor test battery. The test battery (Table 1) was initiated after the subject entered the test room and was seated at a desk. Computer-based tests were implemented in the LabVIEW G programming language (National Instruments Austin TX) running on a Sony Vaio PC laptop (reaction time, perspective taking, match to sample, manual tracking and dual tasking -the order of these tasks were randomized), or on the simulator control computer (motion perception).
The Stanford Sleepiness scale was used to quantify subjective changes in sleepiness 30 . Subjects were asked to choose an ordinal value from a list of statements that best described their state of sleepiness: 1. Feeling active and vital, alert; wide awake 2. Functioning at a high level, but not at peak; able to concentrate 3. Relaxed; awake; not at full alertness; responsive 4. A little foggy; not at peak; let down 5. Fogginess; beginning to lose interest in remaining awake; slowed down 6. Sleepiness; prefer to be lying down; fighting sleep; woozy 7. Almost in reverie; sleep onset soon; lost struggle to remain awake Static Visual Acuity was assessed using a Landolt 'C' eye chart positioned 3.05 m (10 feet) away at eye level. Subjects indicated the orientation of the opening of the 'C' (left, right, up or down) along a line of 5 characters, www.nature.com/scientificreports www.nature.com/scientificreports/ typically starting at 10/10 (logMAR = 0). Visual acuity was determined as the smallest line on which the subject could correctly identify the orientation of at least 3 'C' optotypes.
Manual dexterity was assessed with the Purdue Pegboard 31 test (Lafayette Instrument, Lafayette IN). Subjects were tasked to place as many pins in a vertical row of slots (one at a time) within 30 s, first with the right hand, then with the left. The pins were then removed and subjects asked to place pairs of pins (with both hands simultaneously) in two vertical rows of slots within a 30 s period.
Simple reaction time was assessed by having the subject press the left mouse button as soon as possible after a circular icon appeared on a black screen 32 , based on the Simple Reaction Time task in the Automated Neuropsychological Assessment Metrics (ANAM -Vista Life Sciences, Washington DC). Preemptive presses were counted but ignored in the reaction time calculation. Total test time was 60 s. A computerized perspective taking task 32 was developed based on the Directional Orientation Test from the Test of Basic Aviation Skills, used by the US Air Force to assess potential pilot recruits 33 . In a previous study we found a significant adverse effect on perspective taking during Galvanic vestibular stimulation 32 , an analog of post-flight sensorimotor dysfunction in astronauts [34][35][36] . A topographical map was shown on the left of the screen with an aircraft icon at the center, heading in one of the four cardinal directions (north, south, east, or west). Subjects were instructed to imagine they were piloting this aircraft, and were asked to indicate a cardinal direction (e.g. 'Which direction is East?') relative to a larger aircraft image on the right-hand side of the screen using one of the four arrow keys. Participants performed 32 trials. Time to complete each task and number of correct responses were recorded.
Short-term memory for learned associations was assessed with the match to sample task 32 , based on the ANAM module. Subjects were instructed to memorize a single 4 × 4 array of blue and red squares presented for 2 seconds. After a 2-second delay two 4 × 4 patterns appeared on the screen, one of which matched the previously viewed array. Subjects were instructed to identify the matching pattern by pressing the corresponding right or left arrow key on the computer keyboard. The task consisted of 20 trials.
Manual tracking -subjects were required to use the computer mouse with their dominant hand to maintain a cross-hair target inside a 15mm-diameter circle moving at 20 mm/s on the computer screen and randomly changing direction over a 60 s epoch 32 . www.nature.com/scientificreports www.nature.com/scientificreports/  www.nature.com/scientificreports www.nature.com/scientificreports/ Dual tasking -subjects performed the tracking task above whilst responding to prompts from a second computer monitor for a 4-digit numerical code to be entered on a keypad with the non-dominant hand. The distracting task was performed continuously, and the time to respond and the number of correct responses were recorded, in addition to tracking performance.
The motion perception task was performed with the subject in the motion simulator ( Fig. 1; described in the following section), seated and restrained with a harness and foam head-holder. Subjects were asked to close their eyes (verified verbally by the operator) and indicate gravitational vertical with the control stick while the cabin moved in a pseudorandom manner driven by a sum of seven sines with frequencies at 0.12, 0.25, 0.32, 0.43, 0.62, 0.80 and 0.98 Hz, first in roll for 60 s, then, after a short break, in pitch. Control stick orientation was acquired at 50 Hz throughout the period of motion.
Motion simulator. The motion simulator ( Fig. 1) was based on a 6 degree-of-freedom Stewart platform (V7, CKAS, Melbourne, Australia). A cylindrical polypropylene water tank (2.2 m diameter; 1.7 m height) formed the cabin, and was attached to a 50 mm thick plywood base bolted to the motion platform. Three ceiling-mounted short-throw digital projectors (BENQ 515ST) provided a 180° field-of-view display. Subjects were placed in a racing seat and restrained by a 4-point harness (Corbeau A4, USA). The control pod included a steering wheel (Trackstar 6000, ECCI, Mineapolis, MN) control stick (CH Products, Vista, CA), and pedals (Trackstar 6000, ECCI, Mineapolis, MN).
Choice of simulation tasks. The major methodological constraints for this study were the time available for training the crew on the test battery and simulator tasks (90 minutes maximum per subject) and the duration of the critical R + 0 testing session (45 minutes total including the test battery and full-motion simulations). This restricted the number, duration and complexity of simulator tasks and necessitated an approach focusing on tasks on which the crew were already experienced (i.e., minimal training required). The investigators opted for a driving task (post-landing recovery of driving ability was of considerable interest to NASA's medical branch), a T38 Talon landing simulation (the majority of astronaut subjects were veteran military test pilots with T38 experience), and, at NASA's request, a Mars Rover simulation based on the prototype Space Exploration Vehicle 37 . In this report we describe the results from the driving simulations. www.nature.com/scientificreports www.nature.com/scientificreports/ Driving simulations. All subjects performed a mountain road and cone course driving simulation, implemented using commercial software (rFactor, Image Space, Ann Arbor, MI). For the mountain course subjects were required to drive a car (Lexus ISF) along 3 km of twisting mountain road (Fig. 2a -based on an open source circuit 'Harugahara' 38 ) as quickly as possible while maintaining their position within the right lane. Data files were processed in LabVIEW to provide the position of the vehicle (left front tire) relative to the center line (Fig. 2b-d).
The number of lane crossings, the time to correct (return to the right lane after each crossing) and the percentage of time spent in the wrong lane, were calculated, as well as mean and peak speed for each trial.
The cone course was implemented using a commercially available track development tool (Bob's Track Builder, bobstrackbuilder.net). Three sets of cones (numbering 10, 9, and 11 cones) were situated on a straight 1500 m section of road (Fig. 3). The space between cones averaged 30 m, and the distance between sets of cones was approximately 220 m. Subjects were instructed to drive as quickly as possible whilst slaloming around the cones without hitting them. The time to complete the course and the number of cones hit were calculated. www.nature.com/scientificreports www.nature.com/scientificreports/ sleep restriction protocol. Sleep-restricted subjects performed a scaled-down protocol consisting of the sleepiness scale, manual tracking and dual tasking, and the driving simulations. Prior to the final 'S + 0' test session subjects in the sleep portion of the study underwent a 30-h period of sleep deprivation. At selected time points throughout the sleep restriction period, subjects participated in a short psychomotor vigilance test 39 and recorded their sleepiness rating and activities in a worksheet on a tablet computer, the results of which were uploaded to a secure website to monitor compliance with the sleep restriction protocol. These tests were conducted at baseline when the subject awoke on the day before testing, at 5-h intervals for the first 10-h block, at 2-h intervals during the second 10-h block, and 1-h intervals during the final 10-h block, for a total of 18 tests. During the last 10 hours of sleep restriction subjects were asked to limit caffeine consumption, refrain from operating a vehicle or machinery, or participating in strenuous activities. The final vigilance test and worksheet at hour 30 were completed in the laboratory just prior to conducting the final 'S + 0' test session.

statistics.
Due to the small data sets, a non-parametric single-tailed Mann-Whitney U test was implemented in SPSS (IBM Corporation, Armonk, NY) to determine if day of landing (R + 0) data changed significantly (p < 0.05) compared to preflight data; single-tailed as based on post-flight changes reported in the literature and our own previous experience, we hypothesized that long duration spaceflight would only impair astronaut function post-flight (i.e., we were not expecting improved performance on landing day compared to pre-flight).

Results
No significant post-flight changes were observed in reaction time, perspective taking, match to sample, manual tracking or static visual acuity (Table 2). Crewmembers' self-reported sleepiness was significantly higher (U = 30; p = 0.001) on landing day (R + 0) relative to the pre-flight baseline, and was comparable to the significant increase in sleepiness (U = 12; p = 0.000005) observed in the sleep group after the 30-h sleep restriction protocol (Fig. 4a). Although there was no increase in error on R + 0 during the manual tracking task alone, when a distracting (dual) task was added there was a significant increase (U = 43; p = 0.03) in mean tracking error in the astronaut group, which was not observed in the shadow or sleep groups (Fig. 4b). The astronauts alone also exhibited a small but significant decrease in manual dexterity on R + 0 for the left (non-dominant) hand (U = 33; p = 0.002; Fig. 4c), and the reduction in inserted pins was just above the threshold of significance for the right hand (U = 63.5; p = 0.08) and for both hands simultaneously (U = 60; p = 0.06). These post-flight changes in the astronaut group had returned to pre-flight levels by four days after landing (R + 4; Fig. 4). The astronauts exhibited a significantly reduced response (U = 47; p = 0.016) to pitch cabin motion at the lowest frequency (0.12 Hz) on landing day during the motion perception task (Table 3 and Fig. 5), and there was a tendency towards a blunted response on R + 0 in both pitch and roll for frequencies of 0.43 Hz and below. There was no consistent changes in roll or pitch perception in the shadow group (Table 3).
There were profound deficits in post-landing driving performance for the 3 km winding road simulation in the astronaut group (Table 4). Pre-flight and landing day performance from one crewmember demonstrates a significant post-flight loss of vehicle control, with many more deviations onto the wrong side of the road (Fig. 6). This was consistent across the eight astronauts on R + 0, with significant increases in lane crossings (U = 35.5; p = 0.003; Fig. 7b), time to recover (U = 37; p = 0.004; Fig. 7c) and time spent in the wrong lane (U = 13; p = 0.00003; Fig. 7d). Astronaut driving performance recovered to baseline by four days after landing (R + 4). There were no changes in mountain driving performance in the shadow group or in the sleep group following the 30-h sleep restriction protocol (Table 4 and Fig. 8). There were no significant changes in driving performance on the cone driving task for the astronaut, shadow and sleep restriction groups (Table 5).  Table 3. Results from the motion perception task (peak power). Significant changes shown in boldface.

Discussion
Cognitive/sensorimotor test battery. The results of this study demonstrate subtle but significant changes in cognitive/sensorimotor performance on the day of return (R + 0) from ISS missions that adversely affected operator proficiency. Self-reported sleepiness, unsurprisingly, was higher in the astronauts on landing day. There was a small but significant decline in manual dexterity, and manual tracking performance during dual tasking was significantly impaired. Although not conclusive, there was some evidence of a degradation in motion perception at frequencies below 0.43 Hz. None of these changes were observed in the shadow group. The sleep cohort, who reported a significant increase in sleepiness after the 30-h sleep restriction protocol analogous to the astronaut group, did not exhibit impaired tracking during dual tasking. These findings demonstrate that, with the exception of subjective sleepiness, the changes in performance on the cognitive/sensorimotor test battery observed in the astronaut group on R + 0 were likely due to factors associated with spaceflight, rather than simply fatigue alone or lack of practice. The mild sensorimotor effects (manual dexterity declined by around 10%) suggest a general post-flight malaise in motor function www.nature.com/scientificreports www.nature.com/scientificreports/ and motion perception. Adding a distracting task significantly impaired manual tracking performance, indicating post-flight limitations in available central processing resources in the astronauts; a lack of cognitive reserve apparent only when faced with competing tasks. In isolation, none of these spaceflight-induced changes suggest major cause for concern; however, as discussed below, taken together they significantly affected operator proficiency.
Driving performance. The ability to maintain lane position during the mountain driving simulation was significantly impaired in astronauts on R + 0. Crewmembers made more crossings into the wrong lane, took longer to correct, and spent a greater percentage of time in the wrong lane compared to before flight. These changes were not observed in the shadow or sleep cohorts, which strongly suggest that the degradation in astronaut driving performance was related to spaceflight rather than fatigue alone.
Performance on the cone course was unaffected in all three cohorts. One possible explanation may be the different frequency characteristics of the mountain and cone driving tasks. Slaloming about the cones induced rapid changes in the orientation of the gravito-inertial acceleration (GIA) vector (the sum of gravity and centripetal acceleration, utilized by the brain to perceive tilt 40 , simulated by roll tilts of the cabin) in the coronal plane at a frequency of around 0.3 Hz. The large curves on the mountain course generated GIA tilts at much lower frequencies (<0.05 Hz). Motion perception was impaired at very low (tilt) frequencies in the astronaut group on landing day, thus it may have been harder for crewmembers to maintain a long sweeping curve on the mountain course as opposed to a rapid oscillation of the vehicle about the cones. time course of recovery. Performance decrements in manual dexterity, dual tasking and motion perception observed in the astronaut group on R + 0, and subjective sleepiness, recovered by the second post-flight session (3-5 days post-landing). Lane control on the mountain driving course also recovered by R + 4.     www.nature.com/scientificreports www.nature.com/scientificreports/ and is a direct measure of low-frequency otolith function. We found a significant post-flight reduction in OCR gain in 25 cosmonauts that persisted up to 5 days after return from the ISS 11 . The human tilt response is frequency limited to approximately 0.33 Hz 12 , and the motion perception results from the current study demonstrated evidence of a reduction in sensitivity to roll and pitch motions of the cabin at low frequencies, consistent with flight studies showing impairment in low-frequency otolith function. Post-flight blunting of the tilt response would affect operator proficiency on tasks that require perception of or alignment with tilted visual or inertial cues, such as the mountain driving course.
Fatigue is likely a factor in post-flight performance decrements, but the results of the sleep restriction study suggest that sleepiness alone was not responsible. Astronauts were sleepier on R + 0 but reaction time was unchanged, so subjects could attend to a task for short periods despite their fatigue. The impairment in manual dexterity perhaps reflects persistence of in-flight adaptation of fine motor control to microgravity that is maladapted to the terrestrial environment. However, the reduction in the number of pins placed on landing day was less than 10%, and it seems unlikely that the dramatic post-flight inability to maintain lane control was due primarily to 'finger trouble' . The degradation in manual tracking during dual tasking points to post-landing limitations in cognitive processing resources that were unique to the astronaut cohort. The results do not support a vestibular basis for this post-flight dual-tasking impairment. Cognitive tasks that utilized cortical areas receiving vestibular input 32 , such as perspective taking (parietal-temporal junction and superior parietal lobule) and match-to-sample (hippocampus), were unaffected on R + 0 (Table 2). Moreover, performance on the same dual-tasking paradigm was unchanged by application of pseudorandom Galvanic vestibular stimulation in a recent ground study 32 .
The post-flight impairment of operator proficiency may also be related to environmental factors unique to spaceflight. The partial pressure of CO 2 on the ISS, averaging slightly less than 4 mm Hg over a 7-day period 41 , is considerably higher than on Earth (0.3 mm Hg), and elevated CO 2 levels have been linked to an increased probability of headache in ISS crewmembers 41 . However, current US Environmental Protection Agency guidelines state that the maximum exposure limit is indefinite at CO 2 levels below 7.6 mm Hg 42 . The altered light-dark cycle, sleep deprivation, high mental and physical workload of astronauts, all experienced in a confined space, have been simulated in laboratory studies such as Mars520, in which 6 male subjects lived and worked in a 550 m 3 facility (a little more than half the volume of the ISS) from June 3 rd 2010 until November 4 th 2011. Subjects were found to exhibit decreased cortical activity associated with sensory deprivation and monotony, and diminished sleep quality, although any functional impact on cognition and operator proficiency was not elucidated 43 . Similarly, studies of cognitive performance in personnel over-wintering in Antarctica found no significant changes 43 .   www.nature.com/scientificreports www.nature.com/scientificreports/ Taken together, the results suggest that a range of subtle physiological changes in spaceflight combine to leave astronauts vulnerable to performance decrements on the day of landing, particularly when faced with low-frequency GIA or visual tilts and multiple and competing task requirements. A striking feature of our results is the disparity between the subtle nature of the changes observed in astronaut performance on the cognitive/ sensorimotor test battery on landing day and the profound impact these changes had on operator proficiency. It is difficult to imagine a direct causative link between any single test deficit observed in this study and the observed impairment in driving ability; say, for example, the 10% decrease in manual dexterity and the inability to maintain lane control. Moreover, it is also difficult to imagine that addressing any single deficit, such as an in-flight program that maintained manual dexterity at pre-flight levels, would significantly improve post-flight operator proficiency. Our results suggest that countermeasure development should target the cumulative effect of the subtle physiological changes observed on landing day, rather than focusing on individual cognitive or sensorimotor impairments. Based on our results, the following countermeasure recommendations were made to NASA's Mission Architecture Team: • In-flight high-fidelity 'just-in-time' refresher training for landing and post-flight manual control tasks • Improved displays/non-visual aids to support crewmembers during manual control maneuvers with a tilt component (visual or gravito-inertial) • Cognitive/sensorimotor self-assessments to gauge fitness for duty before conducting challenging manual control tasks • Consider limitations in dual tasking when assigning crewmember assignments during critical stages of manual control