STEM Today

JANUARY 2016, N O 4

STEM Today

Cover Image Astronaut Clayton C. Anderson Image Credit: JSC2009-E-286653 (3 Nov. 2009) — NASA astronaut Clayton C. Anderson, mission specialist

Biography Page NASA Unveils Celestial Fireworks as Official Hubble 25th Anniversary Image The sparkling centerpiece of Hubble’s anniversary fireworks is a giant cluster of about 3,000 stars called Westerlund 2, named for Swedish astronomer Bengt Westerlund who discovered the grouping in the 1960s. The cluster resides in a raucous stellar breeding ground known as Gum 29, located 20,000 light-years away from Earth in the constellation Carina.

Image Credit: NASA, ESA, the Hubble Heritage Team (STScI/AURA), A. Nota (ESA/STScI), and Westerlund 2 Science Team

STEM Today , January 2016

IN THIS EDITION Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight Long duration spaceflight alters sensorimotor function which manifests as changes in eye-head-hand control, postural and/or locomotor ability, gaze function, and perception. These changes have not specifically been correlated with real time performance decrements. The risk of impairment is greatest during and soon after G-transitions when performance decrements may have high operational impact (landing, immediate egress following landing).

The possible alterations in sensorimotor performance are of interest for Mars missions due to the prolonged microgravity exposure during transit followed by landing tasks.

Gap’s in NASA’s Human Research Roadmap

1. Determine the changes in sensorimotor function over the course of a mission and during recovery after landing.

2. Determine the effects of long-duration spaceflight on sensorimotor function over a crewmember’s lifetime.

3. Determine if sensorimotor dysfunction during and after long-duration spaceflight affects ability to control spacecraft and associated systems.

4. Determine if there are decrements in performance on functional tasks after long-duration spaceflight. Determine how changes in physiological function, exercise activity, and/or clinical data account for these decrements.

5. Determine if the individual capacity to produce adaptive change (rate and extent) in sensorimotor function to transitions in gravitational environments can be predicted with preflight tests of sensorimotor adaptability.

6. Determine if exposure to long-duration spaceflight leads to neural structural alterations and if this remodeling impacts cognitive and functional performance.

7. Determine the most optimal pharmacological and sensorimotor countermeasure combination that reduces Space Motion Sickness (SMS) while minimizing side effects.

8. Develop a sensorimotor countermeasure system integrated with current exercise modalities to mitigate performance decrements during and after spaceflight.

Special Edition on Sensorimotor Alterations Associated with Spaceflight

Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight NASA’s Human Research Program (HRP) has identified a number of potentially significant biomedical risks that might limit to the agency’s plans for future space exploration, which include missions back to the Moon and on to Mars.

Among them is the: "Risk of Impaired Ability to Maintain Control of Vehicles and Other Complex Systems," which is described as follows: "Space flight alters sensory-motor function, as demonstrated by documented changes in balance, locomotion, gaze control, dynamic visual acuity, eye-hand coordination, and perception. These alterations in sensory-motor function affect fundamental skills required for piloting and landing airplanes and space vehicles, driving automobiles and rovers, and operating remote manipulators and other complex systems. However, relationships between the physiological changes and real-time operational performance decrements have not yet been established, owing to both the inaccessibility of operational performance data and the presence of confounding, non-physiological factors in most known instances of significant operational performance decrement. While space flight induced alterations in sensory-motor performance are of concern for upcoming lunar missions, they are of greater concern for Mars missions due to the prolonged microgravity exposure during transit, which will more profoundly affect landing task performance and subsequent operation of complex surface systems."

Control of vehicles and other complex systems is a high-level integrative function of the central nervous system (CNS). It requires well-functioning subsystem performance, including good visual acuity, eye-hand coordination, spatial and geographic orientation perception, and cognitive function. Evidence from space flight research demonstrates that the function of each of these subsystems is altered by removing gravity, a fundamental orientation reference,which is sensed by vestibular, proprioceptive, and haptic receptors and used by the CNS for spatial orientation, navigation, and coordination of movements. The available evidence also shows that the degree of alteration of each subsystem depends on a number of crew- and mission-related factors.

Neurovestibular Experiments Conducted During Space Flight

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Space Flight Evidence Crew Verbal Reports A number of (unpublished) crew verbal reports were obtained early after flight by some of the authors . While difficult to combine, owing at least in part to the lack of standardized questions and structured interview techniques, these reports are informative in that they provide insight into the individual crewmember perceptions.

As an example, the following transcript (obtained by Dr. Reschke) captures impressions from a Shuttle commander obtained immediately (<4 hrs) after flight. The discussion focused on target acquisition tasks the commander performed for Dr. Reschke during the flight and his difficulties with nausea, disorientation, posture, locomotion, etc. after the flight (italicized text indicates the crewmember’s responses to the Dr. Reschke’s questions).

Did you try to limit your head movements? Oh yes, definitely. When you were trying to acquire the targets only, ...did you notice any difficulty in spotting the targets? Oh yeah, oh yeah. Did it seem as though the target was moving or was it you? I felt that it was me. I just couldn’t get my head to stop when I wanted it to. So it was a head control problem? Yeah, yeah in addition to the discomfort problem it caused. So when you first got out of your seat today, can you describe what that felt like? Oh gosh, I felt so heavy, and, uh, if I even got slightly off axis, you know leaned to the right or to the left like this, I felt like everything was starting to tumble. When you came down the stairs did you feel unstable? Oh yeah, I had somebody hold onto my arm. Did you feel like your legs had muscle weakness, or ... was it mainly in your head? It was mainly in my head.

Every crewmember interviewed by one of us on landing day (>200 crewmembers to date) has reported some degree of disorientation/perceptual illusion, often accompanied by nausea (or other symptoms of motion sickness), and frequently accompanied by malcoordination, particularly during locomotion. Of particular relevance to the ability to perform landing tasks, common tilt-translation illusions (see below) include an overestimation of tilt magnitude or misperception of the type of motion. Most also reported having experienced similar symptoms early in flight; however, except in the most severely affected, there seems to be no correlation between the severity of the symptoms following ascent and those following descent. The severity and persistence of postflight symptoms varies widely among crewmembers, but both tend to decrease with increasing numbers of space flight missions.

However, both severity and persistence increase with mission duration. Symptoms generally subsided within hours to days following 1-2 week Shuttle missions but persisted for a week or more following 3-6 month Mir Station and ISS missions. The degree to which these psychophysical effects might affect piloting skills is difficult to judge, as recent, intensive training may have offset any impact on Shuttle landings, especially under nominal engineering and environmental conditions, and long duration Mir and ISS crewmembers to date have only piloted ballistic entry spacecraft, which parachute in, allowing no human control inputs during the last 15 min before landing.

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Shuttle Entry and Landing Spatial Disorientation Shuttle landings, to date, have all been successful, but landing performance has been more variable than desired. The timing and shape of the commander’s control input during the flare depends critically on correct perception of speed, altitude, attitude, and sink rate. The flare maneuver, in turn, determines the readily measurable landing performance metrics, such as touchdown sink rate, speed, and distance. Of all the landings between STS-1 and STS-108, the Shuttle crossed the runway threshold abnormally low 20 times.

Seven landings touched down abnormally long or short, and 13 had high touchdown sink rates, with three exceeding the 5 ft/sec structural limit. Moore et al. reported that touchdown speeds during the first 100 Shuttle landings varied widely, with 20% outside of acceptable limits and six equaling or exceeding the maximum speed of 217 knots/hr (main landing gear tires are rated at 225 knots/hr maximum speed). They also note that the fastest landing on record (224 knots/hr) was linked to the commander’s momentary spatial disorientation , as was the second fastest (220 knots/hr).

Normally, commanders perform better than this when flying the STA and the flight simulators. A different analysis of Shuttle landing compared piloting performances in terms of sink rate at touchdown. Fig. 1 shows preflight performances flying the STA and subsequent postflight performances in the Shuttle by commanders of all missions from STS-43 to STS-108. The average STA and STS touchdown sink rates were similar, and almost all STA touchdown sink rates fell in the desirable range; however, the STS touchdown sink rate distribution exhibits greater variability, with more than 10% exceeding the desired sink rate at touchdown.

The landing of the eightday STS-3 mission in 1982. The commander, who was flying visually, took over manual control of the vehicle 30 seconds before landing at White Sands, NM. The vehicle was decelerating at 0.25 g. Starting at flare, when the commander attempted to lower the nose of the Shuttle, the vehicle exhibited a pilot induced oscillation (PIO) of three full cycles with increasing amplitude that continued through touchdown.

Post-flight analysis showed no engineering anomaly in the flight control system. The commander was a highly experienced test pilot, very familiar with conventional PIO and with the 0.25g deceleration of landing. However, it is possible that he underperceived his pitch attitude because of tilt-translation ambiguities and caused the PIO by making larger control stick movements than necessary to compensate for the misperception. This could have been further exacerbated by inappropriate manual control inputs to the stick caused by miscalibration of eyehand coordination.

In a recent interview, however, the commander denied having any issue with PIO, or misinterpreting pitch attitude. His recollection was that the nose came down earlier than expected as the Shuttle began to slow down.

He said the stick was not responsive when he first attempted to pitch the nose back up, but then it seemed to over-respond and pitched up more than he expected. Because he was then concerned about a potential problem with the stick, he brought the nose down and left it down. The commander’s recollection appears to be consistent with the landing video, but not with data from the control stick that showed five large amplitude reversals in the pitch plane command after main gear touchdown. While difficult to reconstruct so long after the event, this may be noteworthy as an unrecognized case of spatial disorientation in a highly experienced pilot.

Increasing pilot awareness of the PIO problem, modifying software to reduce control authority automatically when oscillatory control outputs are detected, adding a heads-up display (HUD) pitch attitude read-out, and

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Special Edition on Sensorimotor Alterations Associated with Spaceflight restricting landings to low cross-wind and good visibility conditions have so far prevented PIO recurrence. However, it is clear that control phase and gain margins during the landing maneuver are routinely near limits of stability, and that pilots making their first Shuttle landing must overcome disorienting perceptions not encountered during preflight training in the STA.

Flight surgeons now examine every returning Shuttle crewmember for evidence of neurological dysfunction within several hours of landing. Crewmembers are scored for subjective symptoms, coordination, and functional motor performance. McCluskey et al. analyzed data from nine missions, and noted trends, such as a correlation between touchdown sink rate and postflight difficulty performing a sit-to-stand maneuver without using the arms. Scores indicating neuro-vestibular dysfunction generally correlated with poorer flying performances, including a lower approach and landing shorter, faster, and harder.

Apollo Lunar Landing Spatial Disorientation Apollo Lunar Module (LM) had a digital autopilot that on later missions was capable of fully automatic landings. While the Apollo crews used the autopilot through most of the descent, all elected to fly the landing phase manually, using angular rate and linear velocity control sticks to adjust the vehicle trajectory while visually selecting the landing point. Landing sites and times were chosen so that the sun angle provided good visibility, but the crews had problems recognizing landmarks and estimating distances because of ambiguities in the size of terrain features. The vehicles had no electronic map or landing profile displays. The commander flew visually, designating the landing spot using a window reticle, while the second astronaut verbally annunciated vehicle states and status. Unfortunately, the landing area was generally not visible to the crew until the LM pitched to nearly upright at an altitude of about 7000 feet and distance of about 5 miles from touchdown with only 1-2 minutes of fuel remaining.

Spatial disorientation was a concern during landing because visibility was reduced by the window design (views downward and to the right were blocked) and by lunar dust blowback that impaired surface and

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For example, the Apollo 11 and 12 crews reported difficulty in nulling horizontal rates during landing because of blowing dust, and the Apollo 12 and 15 crews reported virtually no outside visibility in the final moments of landing. Visibility was improved in later missions by new hovering maneuvering procedures that reduced blowing dust.

Apollo crews did not acknowledge any spatial disorientation events during landing. They did later admit feeling a little "wobbly" when they emerged to walk onto the lunar surface, but reported that coordination improved steadily during first few hours of lunar ambulation.

Apollo Landing Geographic Disorientation The Apollo LM utilized inertial navigation, updated by occasional star sights, radar orbital data from Earth, and radar altimetry during descent. Nonetheless, there was uncertainty in the accuracy of their computed position as they descended into the landing zone. Since crews could not look straight down, the final approach trajectory to the landing area had to use low angles (16-25◦ ) so crew could see ahead.Mission planners only knew the landing zone terrain to 10 m resolution, so the crews had to confirm visually the LM trajectory and then sight the computer’s anticipated touchdown point using a front window reticle. Given the fractal nature of lunar craters, identification of surface features was challenging.

All six Apollo landings were ultimately successful. However, the Apollo 15 crew experienced geographic disorientation. When they pitched over, they could not identify the craters they were expecting, and the commander had to choose a landing spot in an unplanned area. Maintaining full awareness of the terrain immediately beneath the lander was usually impossible during the final phase of landing, and in one case the LM engine was damaged on touchdown . The Apollo 12 commander encountered heavy dust blowback and said, "I couldn’t tell what was underneath me. I knew it was a generally good area and I was just going to have to bite the bullet and land, because I couldn’t tell whether there was a crater down there or not." He later added, "It turned out there were more craters there than we realized, either because we didn’t look before the dust started or because the dust obscured them."

Apollo 14, landed safely, but on a seven-degree slope. Apollo 15 experienced severe dust blowback that contributed to making the hardest landing of the program (6.8 ft/sec), with the vehicle straddling the rim of a 5 ft deep crater, buckling the bell of the descent engine, and causing an 8 ◦ vehicle tilt. Apollo 16 and 17 experienced less dust obscuration and landed closer to level.

It seems likely that similar problems will be encountered when crews once again begin landing vehicles on the lunar surface. commanders choose to use manual landing modes. The challenge of manual landing is likely to be much greater for Mars landings, owing primarily to the increased transit time in microgravity. A combination of more profound adaptation to microgravity and decreased training recency will likely increase substantially the risks associated with manual landing on Mars.

Rendezvous and Docking Collision between the Progress 234 Supply Ship and the Russian Mir Space Station There were two separate attempts to dock the Progress with the Mir that day. In the first attempt, docking was aborted after the radar used for range calculations apparently interfered with a camera view of the Progress.

In the second, near fatal attempt, mission managers decided to turn the radar off and leave the camera on.

For this arrangement to work the Mir commander asked his two crewmates to look for the Progress approach through a porthole, and once sighted, to provide range information with handheld range instruments. Trouble began when neither the camera view nor the visual spotters could locate the Progress as it closed on the station.

When spotters moved between modules to obtain a better view, they lost their frame of reference, and were uncertain which direction to look. Once spotted, the Progress’ speed was above an acceptable rate, and it was very close to the Mir. Braking rockets on the Progress, fired by the Mir commander, failed to slow the velocity of the approaching spacecraft. No range information or other position data were available to assist the commander. To complicate matters, one of the other crewmembers may have bumped into the commander as he attempted to make last second inputs to the approaching Progress via joystick. The resulting collision tore a portion of the solar panel on the Mir, punched a hole in the Spektr module, and caused a decompression of the station. Members of the Russian Institute of Biomedical Problems (IBMP) believe that the collision between Mir and Progress was caused by poor situational awareness, spatial disorientation, and sensorymotor problems.

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D ID YOU KNOW ?

MOTION SICKNESS ASSESSMENT QUESTIONNAIRE (MSAQ)

Motion sickness is an aversive behavioral state that affects several psychophysiological response systems. Because multiple response systems may be activated by real or apparent motion, an individual is likely referring to a complex set of symptoms when she or he uses the term "motion sick". Moreover, there are individual differences in the extent to which particular motion sickness symptoms (e.g., nausea vs. dizziness) are experienced; and different contexts that cause motion sickness (e.g., visual simulators vs. vehicles) may elicit more or less of a particular symptom. In contrast to the many contributions to the development of a questionnaire that predicts overall susceptibility to motion sickness, there have been fewer contributions to the development of a questionnaire that assesses the experience of motion sickness across a broad range of contexts. The most widely used questionnaire for the assessment of motion sickness is the Pensacola Diagnostic Index (PDI). Other questionnaires for assessing motion sickness include a peer evaluation questionnaire , and the Pensacola Motion Sickness Questionnaire (MSQ). There may be several limitations, however, to each of these questionnaires .

Although the PDI has long been used by many investigators, one limitation of this index is that it yields a single score that depends on the composite magnitude of the following symptoms: nausea, dizziness, headache, warmth, sweating, and drowsiness. These univariate PDI scores imply that motion sickness is a construct that varies along a single continuum, ranging from a slight to severe experience. Alternatively, motion sickness may be better quantified as a multidimensional construct with several symptom components. Such a multidimensional approach was recently employed by Kennedy et al., who used a factor-analytic procedure to develop a questionnaire that assesses the occulomotor (eyestrain, difficulty focusing, blurred vision, headache), disorientation (dizziness, vertigo), and nausea (nausea, stomach awareness, increased salivation, burping) dimensions of simulator sickness.

A similar multidimensional approach was used by Muth et al., who suggested that nausea is not a single symp-

Special Edition on Sensorimotor Alterations Associated with Spaceflight tom, but rather a syndrome comprised of at least three dimensions: gastrointestinal distress (sick, queasy, ill, stomach awareness/discomfort, vomiting), somatic distress (shaky, lightheaded, sweaty, tired/fatigued, weak, warmth), and emotional distress (upset, worried, hopeless, panicked, nervous, scared/afraid).

The primary advantage of these multidimensional approaches is that the syndrome under study may be more accurately assessed in terms of its component parts. In contrast, a single score from the PDI or MSQ could be based on a number of different symptom combinations, which might vary between susceptible individuals and evocative contexts. Therefore, motion sickness may be more appropriately quantified as a multidimensional syndrome rather than a univariate symptom, and more appropriately analyzed via a questionnaire that provides a score for each of its dimensions.

One possible dimension of motion sickness that may not be accurately assessed by current questionnaires is the sopite syndrome . Graybiel and Knepton originally suggested that sopite-related symptoms include drowsiness, yawning, and disengagement from the environment; however, symptoms of negative affect have also been suggested to reflect sopite . To date, symptoms of negative affect have not been included in motion sickness questionnaires such as the PDI and MSQ. Thus, another limitation of motion sickness questionnaires such as the PDI and MSQ is that they may provide a restricted account of the occurrence of sopite-related symptoms.

Reference:

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Gianaros, P. J., Muth, E. R., Mordkoff, J. T., Levine, M. E., and Stern, R. M. (2001). A Questionnaire for the Assessment of the Multiple Dimensions of Motion Sickness. Aviation, Space, and Environmental Medicine, 72(2), 115-119.

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Kennedy RS, Lane NE, Berbaum KS, Lilienthal MG. Simulator sickness questionnaire: An enhanced method for quantifying simulator sickness. Int J Aviat Psy. 1993;3:203-20.

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Muth ER, Stern RM, Thayer JF, Koch KL. Assessment of the multiple dimensions of nausea: The nausea profile (NF) J Psychosom Res. 1996;40:511-20.

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Graybiel A, Knepton J. Sopite syndrome: A sometimes sole manifestation of motion sickness. Aviat Space Environ Med. 1976;47:873-2.

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Matsangas P, McCauley ME. Yawning as a behavioral marker of mild motion sickness and sopite syndrome.

Aviat Space Environ Med. 2014 Jun;85(6):658-61.

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Special Edition on Sensorimotor Alterations Associated with Spaceflight Individual predictors of sensorimotor adaptability There are large inter-individual differences in both the degree of sensorimotor disruption occurring upon initial exposure and in the recovery rate of sensorimotor control upon return to Earth. Oftentimes these individual differences are viewed as noise, i.e., measurement error; however numerous studies have exploited individual variations to better understand the neurocognitive determinants of behavior . Understanding the sources of inter-individual variability would also allow for the generation of customized pre-training and rehabilitation approaches, maximizing crewmember productivity and functional abilities.

Effect of Space Flight on Upper Limb Sensorimotor Function A number of studies of eye-hand coordination have been performed during space flight missions. The following subsections summarize some of the key evidence for eyehand control performance decrements associated with space flight.

Control of Aimed Arm Movements When astronauts first encounter an altered gravity environment, arm movements are often inappropriate and inaccurate. During the Neurolab Space Shuttle mission (STS-90), Bock et al. (2003) performed an experiment in which subjects pointed, without seeing their hands, to targets located at fixed distances but varying directions from a common starting point. Using a video-based technique to measure finger position they found that the mean response amplitude was not significantly changed during flight, but that movement variability, reaction time, and duration were all significantly increased. After landing, they found a significant increase in mean response amplitude during the first postflight session, but no change in variability or timing compared with preflight values.

In separate experiments, Watt (Watt et al., 1985; Watt, 1997) reported reduced accuracy during space flight when subjects pointed to memorized targets. This effect was much greater when the hand could not be seen before each pointing trial. When subjects pointed at memorized locations with eyes closed, the variability of their responses was substantially higher during space flight than during sessions on Earth. In other studies , the investigators found that when crewmembers on the Mir station pointed to targets with eyes open, variability and mean response amplitude remained normal, but the movement duration increased by 10-20% over the course of the mission (flight day 2-162).

Reaching and Grasping Basic tasks such as reaching and grasping were significantly impaired during the Skylab missions. Later, Bock et al. investigated pointing, grasping, and isometric responses during brief episodes of changed gravity, produced by parabolic flights or centrifugation. These experiments provided converging evidence suggesting that during either reduced or increased gravity, the mean amplitude of responses is larger than in normal gravity, while response variability and duration remains unchanged. During the Neurolab Space Shuttle mission, Bock et al.

(2003) found that the accuracy during flight of grasping luminous discs between the thumb and index fingers was unchanged from preflight values, but task performance was slower.

Manual Tracking Changes in the ability of crewmembers to move their arms along prescribed trajectories have also been studied in space. For example, Gurfinkel et al. (1993) found no differences in orientation or overall shape when crew members drew imagined ellipses oriented parallel or perpendicular to their long body axes with their eyes closed. In another study, Lipshits et al. (1993) examined the ability of crewmembers to maintain a cursor in a stationary position in the presence of external disturbances. They found no performance decrements when the disturbances were easily predictable. However, in a follow-on experiment using more complex disturbances, Manzey et al. (1995, 1998) found that tracking errors were increased early in flight, but gradually normalized within 2-3 weeks of exposure to the space environment. Later, Sangals et al. (1999) reported a series of steptracking experiments conducted before, during, and after a 3-week space flight mission. Accuracy was affected only marginally during and after flight. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movement was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. They interpreted these observations as indicating an underestimation of limb mass during flight. No reversals of the in-flight changes (negative aftereffects) were found after flight. Instead, there was a general slowing down, which could have been due to postflight physical exhaustion.

Force Discrimination and Control During a MIR station mission the ability of a cosmonaut to reproduce several positions of a handle from memory was tested. The accuracy with which the handle was set to a given position was reduced; however, the temporal parameters of the movement and the number of discernable handle positions did not change.

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Fine Motor Control Campbell et al. (2005) evaluated the feasibility of survival surgery performed on rats during the Neurolab Shuttle mission. Craniotomy, leg dissection, thoracotomy, laminectomy, and laparotomy were performed as a part of physiological investigations. Surgical techniques successfully performed on rats during space flight include general anesthesia, wound closure and healing, hemostasis, control of surgical fluids, operator restraint, and control of surgical instruments. Although the crew noted no decrement in manual dexterity, the operative times were longer compared with on Earth due to the need to maintain restraint of surgical supplies and instruments.

In another study, Rafiq et al. (2006) measured the effect of microgravity on fine motor skills by investigating basic surgical task performance during parabolic flight. They found that forces applied to the laparoscopic tool handles during knot tying were increased while knot quality was decreased during flight compared with ground control sessions. Also, Panait et al. (2006) studied the performance of basic laparoscopic skills (clip application, grasping, cutting, and suturing) during parabolic microgravity flights. They found that there was a significant increase in tissue injury and task erosion and a decreased trend in the number of tasks successfully completed.

Dual Tasking and Manual Performance Manzey et al. (1995, 1998) investigated motor skills in space under dual-task conditions in single case studies.

They found interference between a compensatory tracking task and a concurrent memory search task to be greater in space than on Earth. The elevated interference was greatest early in flight, but gradually normalized, reaching the preflight baseline only after about 9 months in orbit. In one of these studies, Manzey et al. (1995) also found that task interference was independent of the difficulty of the memory search task, suggesting that the critical resources affected were probably not those related to memory, but rather those pertinent to motor control (both tasks required an immediate motor response). Bock and colleagues have also shown that motorcognitive dual tasking costs are higher during microgravity portions of parabolic flight and when crewmembers are on the International Space Station . In the latter case, manual tracking of a target was particularly affected by concurrent performance of a rhythm production reaction time task, suggesting that complex motor planning resources are particularly affected by spaceflight.

The laboratory tasks described above might actually underestimate the impairments with microgravity as many differ from real-life scenarios. For example, it was reported that microgravity slowed aimed arm movements by 10-30% on experimental tasks, but time and motion studies of routine activities on Skylab documented up to 67% slower movements in microgravity than on Earth.

Effect of Space Flight on Posture and Locomotion Movements are adapted during spaceflight, but this microgravity adaptive state is subsequently inappropriate for a gravitational environment so that astronauts must spend time readapting to Earthâ&#x20AC;&#x2122;s gravity following their return. During this readaptation period a number of studies performed at Dr. Bloombergâ&#x20AC;&#x2122;s Neuroscience motion laboratory at NASA/JSC have shown disruption in astronautsâ&#x20AC;&#x2122; spatial coordination abilities during walking .

Additionally, short and long duration spaceflight show effects of maladaptation during walking on a treadmill upon return to Earth, evidenced as increased variability of muscle activity.

Further, during this treadmill walking test subjects showed modified lower limb kinematics, including increased variability in the support limb kinematics at heel strike as well as the motion of the knee during the double support phase . Further, these subjects also demonstrated disruption in head-trunk coordination after both short and long duration space flight . A more recent study has reported reduction in visual acuity during walking, supporting that the outcome of this increased variability in lower limb muscle activation, limb kinematics, headtrunk, and eye-head coordination after space flight is manifested as the inability to stabilize images on the retina during dynamic perturbations such as walking. From a functional perspective we have shown that these postflight changes contribute to impairment in mobility on a functional obstacle course and decrement in the ability to coordinate effective landing strategies during a jump down task . One of the hallmark observations concerning tests of astronaut sensorimotor function is the inherent variability in both the degree of disruption and the recovery rate between subjects. Inter-subject variability in adaptive capability may account for the divergent results observed between individuals. At present we cannot predict preflight which individual astronauts will experience the most significant sensorimotor disturbances.

Behavioral Predictors Sensory Bias Subjects who rely more on vision for control of movement have more difficulty adapting their walking and postural control strategies in new environments, indicating that visual dependency may predict decreased ability to adapt to novel environments . Interestingly, Lex et al. (2012) found that individual differences in cognitive representations of movement direction were associated with rate of adaptation on a visuomotor adaptation task.

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Special Edition on Sensorimotor Alterations Associated with Spaceflight Participants were asked whether pairs of movement directions were similar or not. Those that made judgments reflecting a global cognitive representation of movement directions that was aligned to cardinal axes were faster adapters. In contrast, subjects that made judgments reflecting local cognitive representations that were aligned to neighboring directions were slower adapters.

Computerized dynamic posturography (CDP) tests, which can determine the extent to which an individual effectively uses vestibular, visual, or proprioceptive cues for balance, may also serve as predictive markers of adaptation to spaceflight. Postural ataxia following space flight reflects the adaptive changes in spatial processing of sensorimotor control and the unloading effects of microgravity . CDP has been used to examine postural ataxia following both short-and long duration flights, using the Sensory Organization Tests (SOTs) provided by the EquiTest System platform . The greatest decrements following spaceflight are observed when the subjectâ&#x20AC;&#x2122;s eyes are closed and the support surface rotates in direct proportion to anterior-posterior body sway, disrupting somatosensory feedback, a protocol known as sway referencing . This condition is thus sensitive to adaptive changes in how vestibular feedback is utilized for postural control (SOT5). Most of the crewmembers had increased reliance on feedback from vision during their recovery process as a result of degraded performance of the other two feedback systems during adaptation to microgravity . It has been recently demonstrated that the diagnostic performance of this test was enhanced with the addition of dynamic pitch head tilts.

This finding is consistent with crewmember reports that activities of daily living requiring head tilts are more challenging during post-flight recovery, presumably due to adaptive changes in the multisensory integration of the spatial vertical. In sum, an individualâ&#x20AC;&#x2122;s innate sensory weighting, or the rigidity with which they adhere to a particular sensory weighting, may predict their adaptability to microgravity and subsequent readaptation upon return to Earth.

Behavioral Measures of Individual Motor Learning Responses as Predictors of Adaptability Several studies have examined the time course of motor learning in different training paradigms such as a visual discrimination task or while learning to adapt to either visual or mechanical distortions . The time course of motor learning occurs in two stages: (1) A fast, within-session improvement that can be induced by a limited number of trials on a time scale of minutes.

(2) A slowly evolving, incremental performance gain, triggered by practice but taking hours to become effective.

Two distinct neural systems that differ from each other in their sensitivity to error and their rates of retention have been identified . Separate neural substrates may control the execution of these two motor strategies.

Pisella et al. (2004) reported that a patient with a bilateral lesion of the posterior parietal cortex (PPC) was not able to implement on-line strategic adjustments in response to a prismatic shift in visual feedback during a pointing task, yet showed adaptive after-effects, suggesting that the strategic component was linked to the PPC, and the adaptive component was linked to the cerebellum.

Anguera et al. (2010) showed that cognitive processes such as spatial working memory contributed to the early and not the late stage of sensorimotor adaptation by comparing the rates of adaptation and overlap of the neural substrates underlying these two motor learning stages during a visuomotor adaptation task. Strategic motor control occurs early in the adaptation process once the subject becomes aware of the sensory manipulation and understands on some conscious level how to correct for it .

For example, subjects exposed to a prismatic lateral shift in vision make strategic corrections in pointing movements based on visual feedback to improve performance and eventually point directly to a target . Bock and Girgenrath (2006) investigated the strategic and adaptive realignment components of sensorimotor adaptation of arm aiming movements in response to distorted visual feedback in young and older adults. They found that the recalibration processes were not impaired in older adults compared to young adults, as shown by the magnitude of after effects and transfer of adaptation to novel sensorimotor arrangements, but the strategic processes as represented by improvements during exposure were degraded. These findings support the notion that individual capability for strategic and plastic-adaptive responses shown in behavioral adaptability tests may predict the rate of adaptation to microgravity and re-adaptation upon return to Earth.

Cognitive Factors Visuomotor adaptation involves the recalibration of a well-learned spatial-motor association. There is evidence to support that visuomotor adaptation is cognitively demanding, at least in the early stages . For example, Eversheim and Bock (2001) used dual task paradigms to demonstrate that cognitive resources are engaged in a time-dependent fashion during adaptation: resources related to spatial transformations and attention were highest in demand early in adaptation, while those related to movement preparation were more in demand

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Special Edition on Sensorimotor Alterations Associated with Spaceflight later in learning.

Autors have investigated whether individual differences in spatial working memory capacity relate to the speed of adaptive performance changes in a visuomotor adaptation paradigm . Variation exists in the number of items that individuals can hold and operate upon in working memory , making it particularly amenable to individual differences research approaches. For example, individual differences in working memory capacity have been found to be predictive of math problem solving . Authors investigated the contribution of working memory and other cognitive processes to sensorimotor adaptation by administering a battery of neuropsychological assessments which measured abilities in attention, processing speed, verbal and spatial working memory. Participants also adapted manual aiming movements to a 30 clockwise rotation of the visual feedback display about the central start location. Authors divided the learning curve into "early" and "late" components for each individual.

Authors found that performance on the card rotation task , a measure of spatial working memory, was correlated with the rate of early, but not late, learning on the visuomotor adaptation task. Importantly, there were no correlations between measures of verbal working memory and either early or late learning, suggesting that spatial working memory capacity is a specific predictor of early visuomotor adaptation rate. These findings support the notion that individual differences in spatial working memory capacity may also serve as an effective predictor of spaceflight sensorimotor adaptation success.

Motor Variability Wong and Shelhamer (2014) reported that the rate at which participants adapt saccadic eye movements in response to a double-step target displacement (target location changes during a saccade) was predicted by the extent to which baseline saccade errors were correlated across trials. This suggests that common error detection and correction mechanisms may be at play both in normal motor control and during adaptive modifications to behavior. In a learning to learn paradigm where subjects progressively adapted pointing movements to several different visual distortions across test sessions, authors have reported that participants increase their adaptability; that is, they adapted to each subsequent perturbation faster than control subjects .

Authors found that these subjects were more affected by transient, unlearnable perturbations than controls, however, suggesting that learning to learn may be associated with less stable baseline performance. That is, a strong sensitivity to errors may be beneficial to learning, as long as the environment is consistent and predictable. When environmental changes are transient however, this sensitivity to motor errors would be disadvantageous, potentially resulting in behavioral modifications toward inappropriate goals.

In a recent study, Wu et al. (2014) also reported that faster sensorimotor adaptation is associated with greater baseline variability, particularly in task relevant dimensions. For example, baseline variability related to velocity was predictive of adaptation to a velocity-dependent force field perturbation applied to arm movements. In sum, these studies suggest that baseline measures of motor variability may be useful predictors of subsequent adaptability.

Neural Predictors Brain Activity Participants perform a manual sensorimotor adaptation task and a spatial working memory task in an MRI scanner. Authors found that the neural correlates of early adaptation overlapped with neural substrates that participants engaged when performing a spatial working memory task, notably in the right dorsolateral prefrontal cortex and in the bilateral inferior parietal lobules. There was no neural overlap between late learning and spatial working memory. Authors also tested a group of older adult participants for comparison , and found that across the young and older adults, the extent to which participants recruited the right dorsolateral prefrontal cortex explained individual differences in the rate of early adaptation. That is, the more that participants recruited this brain region, known to be involved in spatial working memory processes, the faster they progressed through the early, strategic stage of sensorimotor adaptation regardless of their age. Engagement of this brain region may be correlated with spaceflight sensorimotor adaptation.

A study by Burke et al. (2014) investigated a number of potential clinical and neural predictors of recovery of lower limb function in patients that have experienced a stroke. They found that the leg Fugl-Meyer score-a clinical scale of function-and the extent of motor cortex that was recruited during movements of the ipsilateral foot (assessed with functional MRI) provided the best predictors of subsequent treatment gains. These findings support the notion that brain activity can provide a useful prediction of future learning/sensorimotor adaptability.

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Special Edition on Sensorimotor Alterations Associated with Spaceflight Brain Connectivity Recent approaches in MRI have been developed to assess brain functional (resting state functional connectivity, fcMRI) and structural (diffusion weighted MRI, DTI) network connectivity, allowing for more integrative assessments of distributed neural systems than in the past. Data acquisition for both techniques is rapid and non-invasive. Moreover, because participants are not performing a task, there are no confounds of the effects of fatigue, attention, or task difficulty that often complicate interpretation of task-driven fMRI studies. FcMRI has proven fruitful for the study of large-scale brain networks in healthy and diseased individuals. Low frequency blood oxygen level dependent (BOLD) signal fluctuations in remote but functionally related brain regions show strong correlations during the resting state . These correlations are highly spatially structured, following known anatomical networks, and are therefore thought to reflect functional connectivity of the human brain. Functional networks that have been identified with fcMRI in healthy individuals by our group and others include motor cortical networks , striatal thalamo-cortical networks , and cerebellar thalamocortical networks.

Resting state network correlations have behavioral relevance. For example, default mode network connectivity is altered following visual or motor learning. Furthermore, the magnitude of corticostriatal network connectivity in Parkinsonâ&#x20AC;&#x2122;s patients is correlated with their motor (putamen networks) and cognitive (caudate networks) symptoms, and is modulated by dopaminergic medication . Moreover, we have documented that greater resting state motor interhemispheric connectivity in older adults is correlated with "motor overflow", or recruitment of the ipsilateral motor cortex during a unimanual task .

Similarly, DTI metrics of white matter tract integrity exhibit network-selective correlations with behavior. For example, white matter integrity underlying the left, but not the right, Brocaâ&#x20AC;&#x2122;s area is correlated with the ability to learn an artificial grammar , while cerebellar white matter fractional anisotropy is correlated with individual differences in the rate of motor learning.

The cerebellum plays a critical role in sensorimotor adaptation . Authors have shown that individual differences in regional cerebellar lobule volumes are predictive of balance scores , and cerebellar network functional connectivity is predictive of sensorimotor and cognitive function in older adults . Studies in patients with cerebellar damage following stroke support involvement of Crus I and lobule V in adaptive improvements with practice, whereas lobules V and VI are linked to aftereffects and retention of adaptation.

Another resting state measure of neural function is corticospinal excitability, measured as the magnitude of a motor evoked potential (MEP) elicited with a transcranial magnetic stimulation (TMS) pulse applied to motor cortex. Interestingly, stroke patients with a lower baseline MEP benefited more from subsequent robotic training . These results, combined with the preceding discussion, support the notion that resting state measures of neural connectivity, excitability, and pathway integrity are predictors of future skill learning. A more thorough elucidation of the neural substrates of microgravity sensorimotor adaptation may yield similar predictive brain network metrics.

Genetic Predictors Genetic polymorphisms have been shown to be associated with factors including neuroanatomical phenotypes such as cortical size or integrity of gray and white matter in the brain and neuroplasticity . Recent findings of genotype associations with dopamine availability in the prefrontal cortex and corticostriatal circuits highlight the role of a single nucleotide polymorphism of the catechole-O-methyltranspherase (COMT) gene at codon 158/108. The substitution of a Valine (val) with Methionine (met) allele at this codon (G to A) results in reduced COMT enzymatic activity, which leads to less dopamine degradation and higher prefrontal dopamine availability . COMT met homozygotes show comparatively better performance in working memory tasks and other measures of executive function . In addition to COMT val158met, the DRD2 G > T polymorphism influences dopamine availability by regulating the expression of striatal dopamine receptors. D2 receptor activity in the striatum has been associated with motor control, coordination, and error avoidance . The T allele of the DRD2 genotype (rs 1076560) is associated with reduced D2 expression and consequently with declines in cognitive and motor processing . Individuals who are carriers for the DRD2 T allele show a greater area of activated brain regions and reduced levels of performance in working memory tasks, indicating less efficient neural processing.

Another candidate gene that may be an effective predictor of sensorimotor adaptability is brain-derived neurotrophic factor (BDNF), which is associated with brain derived neurotrophic factor, an important modulator of brain plasticity and learning. BDNF val/met carriers have reduced BDNF in comparison to val/val and have recently been demonstrated to exhibit reduced manual sensorimotor adaptation and less retention of adaptive learning .Variation in the Îą2-adrenergic receptor genetic polymorphism is associated with individual differences in autonomic responses to stress, including susceptibility to motion sickness, an important factor influencing

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Special Edition on Sensorimotor Alterations Associated with Spaceflight functional performance and productivity in spaceflight that has been linked to vestibular system functioning .

Authors evaluated whether a particular DRD2 polymorphism (rs 1076560, G > T), which codes for D2 dopamine receptors in the striatum, is associated with how well patients with Parkinson’s disease respond to exogenous administration of dopamine via L-DOPA . DRD2 T allele carriers of this polymorphism have reduced D2S expression (short isoform of the D2 receptor); thus in comparison G allele carriers have higher D2 receptor availability.

Our hypothesis that Parkinson’s patients who are minor T allele carriers would exhibit a greater benefit of levodopa on early stage motor sequence learning was tested in a behavioral study with 45 Parkinson’s patients.

Patients were tested on two days following a single blind placebo controlled design, with administration of levodopa or placebo pill in a counterbalanced fashion across the two test days. Levodopa improved sequence learning over the level of placebo pill for only the TT and GT patients, whereas GG patients did not show a benefit from levodopa . These findings support the notion that treatment plans for patients with Parkinson’s disease can be enhanced by taking into account measures of endogenous dopamine availability such as genotype.

Similar findings were observed in a study of healthy participants by Pearson-Fuhrhop et al. (2013); individuals with a greater number of beneficial alleles for genetic polymorphisms involved in dopaminergic metabolism exhibit greater motor skill learning gains. Meanwhile, only participants with a lower number of beneficial alleles exhibited improvements in motor learning with levodopa administration.

Recently authors evaluated the proposed role of alleles for genes involved in dopaminergic transmission (COMT val158met, and DRD2 G > T) as an index of individual differences in motor sequence learning and visuomotor adaptation . To test the hypothesis that individuals homozygous for high performance-associated alleles (COMTmet and DRD2-G) would demonstrate faster rates of motor learning and adaptation we tested 70 young adult females. The minor allele groups (val-val for COMT and TT for DRD2) exhibited overall slower reaction time on the motor sequence learning task for both random and sequence blocks, indicating poorer performance but no difference in learning. Of particular interest, we found COMT val-val individuals adapted manual aiming movements to a visual distortion more slowly than met-met or val-met. We also combined COMT and DRD2 polymorphisms into a single model by quantifying the number of "high performance" alleles that each individual carries, and by using non-parametric linear regression we found an association between the rate of sensorimotor adaptation and number of high performance alleles. Thus, one’s genotype for genes involved in dopaminergic metabolism may also serve as a predictor of spaceflight adaptability.

There are not any proven predictive biomarkers of human spaceflight adaptability available at this time. However, the literatures on predictors of motor learning, sensorimotor adaptation, and of functional recovery following stroke suggest several that would be fruitful for future investigation. For example, the BDNF polymorphism and other genes that are involved in dopaminergic metabolism have been linked to manual sensorimotor adaptability.

Cognitive Neuroscience in Space The first studies on space neuroscience go back to 1962 during the Russian Vostok-3 mission, when some sensory-motor studies were carried out. On Earth, new brain imaging techniques, neuropsychological assessment tools and other physiological measures have been developed to enable very detailed studies of brain activity and cognitive functioning. For neuroscientists, as well as psychologists, it is of high relevance to understand the underlying neurocognitive and neuropsychological parameters of space flight. Unfortunately, standard brain imaging techniques (e.g., functional magnetic resonance imaging (fMRI)) are not applicable in space, due to the payload restrictions of space missions and costs. The European module "Columbus", a part of the International Space Station (ISS), was equipped with an electroencephalography (EEG) system as a tool to research the link between weightlessness and central nervous system (CNS) activity. Neurocognitive tests, electrophysiological measurements and other related methods are commonly used in space to assess brain activity, neurocognitive and behavioral status and the mental health of astronauts.

Results from Earth-based research highlight the importance of studying the effects of stress on cognitive performance. Cognitive and perceptual motor performances deteriorate under stress . We can thus expect similar effects in the stressful environment of a space mission and in extreme environments and simulations. Previous work has shown that various psychomotor functions are degraded during space flight, among them central postural functions involving hierarchically organized brain areas, including motor cortex in frontal lobes, basal ganglia, vestibular system in the midbrain and cerebellum, the speed and accuracy of aimed movements associated, among others, with primary motor cortex, cerebellum and visual cortex, internal timekeeping related to prefrontal cortex and striatum, attentional processes distributed in different brain areas, such as frontal and parietal cortex, superior colliculi subcortical region, frontal eye field and anterior cingulate cortex, limb position sense , including the primary somatosensory cortex and cerebellum, and the central management of concurrent tasks involving mainly prefrontal, temporal and parietal cortex and basal ganglia (Figure 1). Such psychomotor

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Special Edition on Sensorimotor Alterations Associated with Spaceflight deficits have been implicated as the causes of accidents in space . It remains unknown to what extent these observed deficits might change during long-term space missions, as on a flight to Mars, for example. Results from Mars-500, one of the longest space mission simulations ever, revealed that a variety of neurological and psychological factors, such as circadian rhythms and social behavior, were affected by characteristics of the mission and the special environment.

Microgravity and Space Motion Sickness Gravity has shaped life on Earth. It is perceived by all organisms, from unicellular forms to humans, determines our orientation in space and helps control posture. We have specialized organs, such as the vestibular system in the inner ear, for gravity perception. Sensory information about motion, equilibrium and spatial orientation is provided by the vestibular apparatus in each ear, which includes the utricle, saccule and three semicircular canals.

The utricle and saccule detect gravity (vertical orientation) and linear movement. The semicircular canals, which detect rotational movement, are located at right angles to each other and are filled with a fluid called endolymph. When the head rotates, the direction is sensed by a particular canal. The endolymphatic fluid within the canal lags behind, due to inertia, and exerts pressure against the canalâ&#x20AC;&#x2122;s sensory receptors. The receptors then send impulses to the brain conveying information about movement. When the vestibular organs on both sides of the head are functioning properly, they send symmetrical impulses to the brain (Figure 2).

Balance information provided by the peripheral sensory organs-eyes, muscles and joints and the two sides of the vestibular system-is relayed to the brain stem. There, it is processed and integrated with learned information contributed by the cerebellum (the coordination center of the brain) and the cerebral cortex (the thinking and memory center). A person can become disoriented if the sensory input received from his or her eyes, muscles and joints, or vestibular organs conflict with one another, and this can produce what is called motion sickness (Table 1). Approximately 70% of astronauts experience space motion sickness (SMS) during the first week of the mission.

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On Earth, gravity is also a neural reference that influences how we perceive an objectâ&#x20AC;&#x2122;s movement and orientation, an ability frequently disrupted in space. For example, moving the head while looking at a control panel can induce the perception that instruments are being displaced . Perception is a cognitive process, and the way we perceive objects in the environment affects our perception of that environment. In space, this is a challenge, due to microgravity. Microgravity alters how we perceive the environment, producing illusory perceptions that have persistent after-effects in astronauts who spend long periods in space. If perception is affected by microgravity conditions, gravity may actually have an inner representation in the brain that is needed for

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Special Edition on Sensorimotor Alterations Associated with Spaceflight important functions, such as proper motor control and motor planning. This has been confirmed by studying the effects of microgravity on covert and overt actions. Furthermore, this inner representation may affect anticipation actions. However, microgravity does not affect verticality perception. Indeed, systematic behavioral observations of the motor behavior of astronauts during short-duration space flight suggest that they preferably align their posture with the vertical polarity of the spacecraft Brain Activity and Sleep in Space Human sleep occurs with circadian (circa = about, and dis = day) periodicity. Circadian clocks evolved to maintain appropriate periods of sleep and wakefulness, in spite of the variable amount of daylight and darkness in different seasons and at different places on the planet. To synchronize physiological processes with the daynight cycle (photoentrainment), the biological clock must detect decreases in light levels as night approaches.

The receptors that sense these light changes include poorly understood cells within the ganglion and amacrine cell layers of the retina that project to the suprachiasmatic nucleus of the hypothalamus. Other structures are also implicated, such as the pineal gland, which synthesizes the sleep promoting neurohormone, melatonin (N-acetyl-5-methoxytryptamine), from tryptophan and secretes it into the bloodstream to help modulate the brainstem circuits that ultimately govern the sleep-wake cycle. Melatonin synthesis increases as light intensity decreases through the night. To study brain activity, especially during sleep, neuroscientists use EEG. The EEG detects abnormalities in the waves and electrical activity of the brain. During the procedure, electrodes consisting of small metal discs with thin wires are pasted on the scalp. The electrodes detect tiny electrical charges that result from the activity of the brain cells. The charges are amplified and appear as a graph on a computer screen or as a printed recording. Sleep loss, fatigue and poor quality of sleep have been reported on numerous space missions.

During the space shuttle era, astronauts usually had between 5-6 h of sleep and lesser in the case of emergencies . On long-duration missions, there can be changes in the quality of sleep. Problems related to this may appear and compromise the performance levels of astronauts . Although the use of drugs is not indicated in general in the aviation work environment, some sleep medication has been used in long-duration missions upon the approval of the medical team. These sleep problems seem to be related to the lack of environmental cues, such as natural light, which produces circadian rhythm disturbances and consequent psycho-physiological effects.

However, other factors, not directly related to the environmental aspects of space missions, may play a role in sleep problems, including anxiety, workload, stress or isolation. Several sleep studies using EEG tests during Columbia and NeuroLab missions showed contradictory results . Sleep patterns were not substantially altered in space compared to prior mission tests; but, a reduction of total sleep was registered, and a clear alteration of circadian cycle was observed.

Cheron et al. examined the alterations of alpha cortical activity during the experience of weightlessness in space and showed an increase of power in the peak alpha frequency (PAF) activity. PAF is the most dominant rhythm in the relaxed, eyes-closed state and is regarded as a marker of cortical activity. Furthermore, this oscillation is considered to be involved in mental and cognitive processes. As there is an inverse relationship between PAF power amplitude and the blood oxygen level-dependent signal , it is hypothesized that the alpha power increase during the stay at the ISS is due to a general lowering of cerebral blood oxygenation of astronauts and cosmonauts undergoing weightlessness, as recently shown by Schneider et al. . Although it has been argued that impairments in cognitive and perceptual motor performance in weightlessness are caused by changes in cerebral blood flow leading to changed electro-cortical signals registered on EEG, there currently is no evidence that a systemic shift of blood volume to the brain during weightlessness is correlated with neural activity.

Consequences of chronic bed-rest depend on the duration and the level of inactivity. As in weightlessness, the circulation is rearranged during the prolonged maintenance of a supine position. Initially, the central blood volume increases; perfusion and hydrostatic pressure in the lower half of the body decreases, and the slightly higher preload and stroke volume can lead to bradycardia, increased renal blood flow and mild polyuria.

Over the course of weeks and months, the plasma volume and the efficacy of orthostatic reflexes regulating blood pressure decrease. When the astronaut is back on Earth again, the low blood volume is insufficient to maintain cerebral blood flow in an orthostatic position. Therefore, orthostatic hypotension may develop and dizziness may appear. A comprehensive return accommodation is required, and astronauts should be monitored for some time after prolonged time in space (Figure 3). Nevertheless, it so far remains unclear whether neurocognitive or neuropsychological impairments and changes are provoked by microgravity itself or by secondary, environmental-related factors. In the first study using low-resolution brain electromagnetic tomography (LORETA) in low gravity , it was demonstrated that the microgravity phases during parabolic flights result in considerable changes in frontal lobe activity, a brain region that is known to play a major role in emotional processing and the modulation of performance

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Space Neuropsychology Among all neuropsychological aspects, attention is one of the most important. Attention is a complex cognitive function that is essential for human behavior. Attention is a selection-based process required to maintain an external (sound, image, smell, etc.) or internal (thought) event at a certain level of awareness. It is not a stable, but, rather, a fluctuating skill. It is not continuously sustained, often subconsciously let up during a task. For a further review, studies on attention were performed during the Soyuz/Salyut (26/6 and T5/7) missions in the 1970s and 1980s .

Other neurocognitive aspects commonly affected in space are spatial orientation, mental rotation and recognition, spatial perception and representation and other perceptual skills (Table 2). Most perceptual problems are related to the microgravity environment characteristics that make astronauts see objects in non-customary orientations. In addition, the interaction of spatial perception with the vestibular system can be a source of conflicts in neural processing, as explained previously. Proper perception of objects may be negatively affected by non-customary orientations. One well-known example is the perception of faces. This problem also exists in space, and it is easy to understand how this may have an effect on face-to-face communication. However, other aspects of perception, such as perceived verticality, as mentioned before, are not affected. This effect is defined as the difficulty of face recognition when a face is inverted.

More recently, research has focused on developing assessment tools to detect and monitor these deficits and problems and counteract them. A decline in attentiveness may primarily occur in space, because of stress-related factors. Problems in attention performance can also indicate the possible compromise of other neuropsychological aspects, such as memory. Having accurate and helpful assessment tools is very important for monitoring performance levels and the mental health of astronauts in space. The unique environmental constraints and characteristics of space have required the development of some specific tools over the years to assess and combat these issues. Moreover, this continues to be an important field of research. Although some now dated cognitive tests and batteries, such as MINICOG or the AGARD test, have been used in space and simulations before. The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is the current standard for this type of assessment in space operations. WinSCAT is a time-constrained test of cognitive abilities, such as attention, math and memory . Right now, WinSCAT is routinely performed by astronauts aboard the ISS every 30 days, before or after their periodic health status test. It is also administered on special crewmembers upon the flight surgeonsâ&#x20AC;&#x2122; request.

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Psychosocial and Neurobehavioral Aspects Astronauts must maintain a high level of performance efficiency over the course of their stay in space. During space missions, astronauts are exposed to an environment that can induce detrimental effects on mood and performance. This is confirmed by a number of studies that report impacts on mood, performance, workload and social aspects of long-term habitation in space . There are thus many reasons to perform neurocognitive assessments in space. The crew has to be prepared in case of any possible events or conditions that may affect neurocognitive performance and subsequently compromise mission success or survival. The unique environmental characteristics of space missions may affect performance, and some of these characteristics are present in simulations. By way of example, during the Mars-500 experiment, subjects experienced isolation, limited space, communication delays with mission control, etc.

Other challenges of great importance that are commonly faced during habitation in space cannot be simulated (e.g., radiation and the impossibility of rescue).

Neurocognitive and neurobehavioral problems occurring in space can be mainly related to four different sources, according to Kanas and Manzey : (1) physical factors, including acceleration, microgravity, radiation and light/dark cycles.

(2) habitability factors, including vibration, noise, temperature, light and air quality.

(3) psychological factors, including isolation, danger, monotony and workload.

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Special Edition on Sensorimotor Alterations Associated with Spaceflight (4) social or interpersonal factors, including gender issues, cultural effects, crew size, leadership issues and personality conflicts.

Cognitive performance should not be separated from broader human social nature. Social aspects play a key role in space missions. Impaired physical and social interactions may result in problems for the crew, especially in long-duration missions. These issues may result in several potentially hazardous conditions, such as a loss of motivation, loneliness, lower performance, depression or other medical conditions . Anecdotal information available from Russian missions reveals that these problems do appear in space missions and are not always very clearly recognized or understood by crewmembers. These aspects have also been studied in analogous situations on Earth.

Regarding psychiatric problems, some evidence is also available from both space missions and analog missions on Earth, such as Antarctic stations and submarine research stations. In these analogous scenarios and simulations, not frequently, but sometimes, we were able to observe how chronic isolation may lead to depression, negative adjustment reactions and psychosomatic problems in members of small teams . In addition, other conditions, like frustration, perceived inability to change things and low light levels, may lead to depression.

The limbic system plays a key role in the emotional responses of mammals and humans. These areas together with frontal cortex and other relevant areas of the brain regulate socio-emotional life and mood. Changes in mood are normal and sometimes may be hard to detect before they evolve into a clinical condition. In small work groups, it may be difficult to perceive these changes in time, and they are usually detected after they already interfere with performance. It is worth noting here that depression may even terminate a space mission, as was the case with Salyut 7 in 1985. Anxiety is also a common problem on Earth, and it has been detected in astronauts on Antarctic missions. It is, however, not common in space missions, though it may appear, as indicated by some Mir missions . The problem with anxiety is its delayed detection. This is why tools for monitoring and treating early symptoms should be researched in greater depth.

The condition known as asthenia is an important issue in mental health in space . It is a controversial topic though, because there is no agreement between space agencies. For Russians, asthenia is a real syndrome, and it is used to describe a set of psychological changes that commonly occur among astronauts. The principle symptoms are fatigue, dizziness, tension headaches, sleep disturbances and/or irritability. In contrast, this diagnosis is not presently recognized in the American DSM . The core feature of all of these syndromes or symptoms is that they may somehow affect the performance of the crew, and we know that lower performance levels may compromise mission success. It is therefore essential that space research pays attention to how these emotional, stress-associated and psychological issues affect cognitive performance, particularly regarding control processes, such as the perception of time , the relationship between automatic and controlled processes (inhibitory processes) and the categorization of incoming information .

Effects of long-duration space flight on target acquisition The need to accurately shift gaze from one target to another, and to maintain the newly acquired image on the retina is a complex process that can be modified, we believe, in part by behavioral requirements that are driven by changes in the environment. For example, it has been previously demonstrated that exposure to the microgravity of space flight induces modification in eye-head coordination during target acquisition . To achieve changes in sensorimotor function, current models of eye-head coordination postulate that a vestibular signal specifying head movement relative to space serves as an integral component underlying saccadic spatial programming when making head-free gaze shifts .

In these models, desired gaze position is compared to an internal representation of actual gaze position. Actual gaze position is derived by summing an efferent copy of eye position in the head with a vestibular and neck motor derived reconstruction of current head position. The difference between desired and actual gaze position produces a gaze position error signal that drives saccadic motor output until the error signal is nullified and the eye movement is stopped. Past studies have supported these models by demonstrating that saccadic eye movements generated in total darkness, successfully acquire a just seen Earth-fixed target after cessation of head angular displacement. Such saccadic eye movements are spatially targeted using remembered semicircular and otolithic vestibular information, respectively. The demonstration of this capability indicates that a functionally meaningful vestibular signal has access to the saccade generating mechanism and may therefore, play a pivotal role in eye-head gaze shifts.

Seven cosmonauts (4 high performance pilots and 3 non-pilots) who had flown between 186-198 days on Mir station served as subjects. The median age of the subjects was approximately 51 yrs. All subjects had the equivalent of an Air Force Class I physical. Study specifics were reviewed by both the Johnson Space Center Committee for the Protection of Human Subjects and the Russian Institute of Biomedical Problems Institutional

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Special Edition on Sensorimotor Alterations Associated with Spaceflight Review Board. Subjects received written and verbal accounts of the test protocol and signed informed consent.

Preflight data were collected four times; 100, 60, 30 and 14 days prior to flight (L-100, L-60, L-30 and L14) and 3 or 4 times postflight (R+1=2 days postflight, R+3=4 days postflight and R+8=7 days postflight).

During each test session the subjects were required to acquire targets that were randomly presented at 20◦ , 30◦ and 60◦ left or right from the central point of fixation with both a head and eye movement using a time

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Special Edition on Sensorimotor Alterations Associated with Spaceflight optimal strategy (acquire the targets as quickly and accurately as possible). Data from a minimum of three and a maximum of five trials for each of the target locations were collected during a test session. The targets were represented by red lightemitting diodes at a distance of 75cm as measured from a class III laser mounted parallel to the target display and projected onto the outer canthus of the right eye prior to testing. All testing was done under normal room illumination. The signal to acquire a target was triggered by a computer generated tone.

At the tone the center fixation point was extinguished and a new peripheral target was illuminated. Following each target acquisition the eyes and head were returned to the center fixation position.

Horizontal eye movements were recorded with nonpolarizing electrodes positioned at the outer canthus of each eye with the reference electrode located on the mastoid process behind the right ear. Head movements were obtained with a tri-axial angular rate sensor mounted on a headband that was attached firmly to the subject’s head. Analog signals from both the eye electrodes and rate sensors were amplified, digitized, and acquired on a computer for subsequent offline analysis.

Results Before flight, all cosmonauts demonstrated a conventional pattern of horizontal target acquisition that consisted of three phases. During the first phase, with a 181-240ms latency, an emerging saccade was directed toward the target. This initial saccade was followed 15-40ms later with a head movement towards the target. During this second phase, gaze reached the target with a joint eye and head movement and the saccadic movement was completed. During the third phase, the head was still moving toward the target, with a compensatory movement of the eyes approximately equal to that of the head permitting gaze stabilization to occur ( Fig. 1).

In spite of this relatively common pattern of gaze stabilization, the variability of the major parameters (peak head, eye velocity and amplitude) was extremely mutable. That is, while there is a common pattern of acquiring specific targets with the head and eye free to move from straight ahead gaze to a new peripheral target; it is believed that trade-offs in head and eye velocities and peak amplitudes can be selectively varied according to a preferred strategy. A simple cluster analysis that involved partitioning the data into related subsets according to flight crew assignment showed two distinct groups (pilot and non-pilot) where unique head and eye movement strategies were used for target acquisition (Table 1).

Specifically, non-pilots employed what was termed a Type-I strategy consisting of high velocity head movements with large peak amplitudes, while pilots used primarily low velocity, small amplitude head movements (Type-II) to acquire the targets (p<0.02). Fig. 1 shows the analog responses recorded for both Types-I and -II strategies before flight and immediately (2+days) postflight. For both strategies peak head velocities increased as the angular distance to the target increased (p<0.01) resulting in greater discrimination between the two distinct strategies for the 60◦ targets (Fig. 2). These differences in peak head velocities were also reflected in the time it took to stabilize gaze.

These data suggest that extended exposure to long duration microgravity affected the target acquisition process substantially. After landing we observed changes in both the amplitude and kinematic parameters for the head and eye movements related to the Type-I and -II strategies. As seen in Fig. 2, and consistent with the newly adopted strategy, during the early stage of recovery after space flight (R+1/+3) peak head velocities for the Type-I group significantly decreased when compared to the preflight values for the 30◦ and 60◦ targets (p<0.02)(Fig. 2-A). Changes in head velocity for the Type-II group showed an increase that was also expressed primarily for the 30◦ and 60◦ targets (p<0.02) (Fig. 2B). When peak head amplitude was examined there was not a significant difference in the 20◦ and 30◦ target compared to preflight. At the same time peak head amplitudes did not change significantly in response to the 20◦ , 30◦ or 60◦ targets (primarily because of the variability across trials) but did show a trend towards significance when acquiring the 60◦ target (Fig. 3).

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Special Edition on Sensorimotor Alterations Associated with Spaceflight In the Type-I strategy group, postflight testing showed a significant decrease in eye velocity compared with preflight performance (p<0.02) for all target locations (Fig. 4A). These changes were largest in response to 60◦ targets. Saccades showed a slight tendency to decrease in amplitude while saccade duration remained fairly constant. For the Type-II group (Fig. 4B) the decrease in peak eye velocity decrease was smaller than that for the Type-I group, but was significant for only the 20◦ targets (p<0.05).

It is interesting to note that while peak eye velocity decreased for all target displacements for both the Type-I and -II strategy groups, the pattern of the decrease has a tendency to be somewhat opposite in nature for the two groups. That is, postflight peak eye velocity for the Type-I strategy has a tendency to decrease from the 20◦ target to the 60◦ target, while for the Type-II strategy, postflight eye velocity tends to increase from the 20◦ to 60◦ target. At the same time saccade amplitudes for both groups showed a non-significant tendency to decrease across all target displacements.

On R+1, latency measurements for the eye and head movements to the 60◦ target increased on averaged by 25-40ms with the exception of the Type-I group in which the head latencies in response to the 60◦ targets increased by 100ms (Fig. 5). A gradual return to baseline values was observed by R+8. Preflight, it ˝ 640ms to stabilize took each cosmonaut 450U their gaze after the presentation of the target.

This time (gaze latency) increased as a function of the angular position of the target (Fig. 6). On the initial days of recovery all cosmonauts took longer for gaze stabilization to occur. For example, on R+1/2 gaze latencies exceeded the cosmonaut’s preflight baseline values ˝ 10 ms. These changes were more charby 110U acteristic of the Type-I strategy for all the target distances. This difference gradually diminished, and by R+8 gaze latencies for the Type I group approached that of the baseline values.

The observation that a particular strategy in acquiring targets was adopted by some cosmonauts, but not all, contributed to the variability in our data samples. Further analysis combining all responses by both groups (Types-I and -II) across all target displacements revealed an interesting pattern of statistical variation related to the different parameters associated with the acquisition of the targets used in this investigation. Specifically, after space flight, the spread in values for eye latency reached 42.6% (vs. 6.67% before flight), and head latency had a value of 37.5% (vs. 14.22% before flight). The range of variation for gaze latency was also increased following flight during the first week to 34.3% (vs. 15.78% before flight). For the head and eye peak amplitudes, the variability decreased after space flight to 24.1% (vs. 44.1% from preflight) for the head and 17.6% (vs.

30.1% preflight) for the eye.

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Overall the data also suggest that regardless of the preflight strategy associated with the acquisition of different targets in the horizontal plane, adaptation to microgravity will drive a change in that strategy. However, authors believe based on the data that the original strategy serves as the base around which change is manifested. It is not possible to identify specific sensorimotor systems that may be responsible for driving adaptation to a space flight environment. However, most believe that the otolith organs and their interactions with the semicircular canals and the muscles controlling movement are the likely candidate associated with the drive for adaptation.

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The increased variability associated with the different parameters of target acquisition during the readaptation process suggests something of a CNS searching strategy. This same finding has been reported by other investigators when describing the adaptation process to space flight (and to simulated microgravity) in the other systems. We can make a supposition that with altered activities of the gravity-dependent sensory systems the normal neural program control of target acquisition precision becomes impossible. Deprived of programmability, target acquisition relies predominantly on feedback which explains the increase of time for task implementation.

Recovery of Functional Sensorimotor Performance Following Long Duration Space Flight (Field Test)

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Special Edition on Sensorimotor Alterations Associated with Spaceflight Gaze Control and Vestibular-Cervical-Ocular Responses After Prolonged Exposure to Microgravity Microgravity does not affect visual function directly. However, because of the altered afferentation from vestibular, support, and tactile-proprioceptive systems, it could lead to disturbances in visual tracking and inhibit the cosmonaut’s activity. Therefore, it is necessary to obtain quantitative evaluations of spaceflight effects upon gaze control and vestibular-cervical-ocular responses.

The study involved 26 Russian crewmembers of the ISS-3 to ISS-24 expeditions from 2001 to 2010. Their ages ranged between 35 and 50 yr, with their average age being 41.5 yr. Length of stay on the ISS was between 129 and 215 d. All cosmonauts had undergone extensive medical examinations (including examination by an ophthalmologist and neurologist), had normal vision with no oculomotor abnormalities, had no known clinical vestibular problems, and were not taking drugs which affect the nervous system.

The study protocol (science experiment "Sensory Adaptation" and clinical-physiological investigation "Vestibular Function Check up") was reviewed and approved in advance by the Bioethics Board of the Institute of Biomedical Problems and Human Research Multilateral Review Board. All cosmonauts gave written, informed consent before participating in the experiment. Data was acquired twice prior to spacefl ight (L-45 and L-30) and after landing on R+1-2, R+4-5, R+8-9, and sometimes R+14-19 where the exact date of examination (for example, R+1 or R+2) depended on landing conditions and health status of the cosmonaut.

Results Spontaneous Eye Movements (SpEM) with Eyes Closed In terms of clinic neurology and according to our accumulated data for postflight examinations,"normal SpEM with eyes closed" means: stable EOG, no spontaneous nystagmus, no slow wave drifts, and no square-wave jerks, no gaze-evoked nystagmus in ’extreme ’ positions. It should be mentioned that even in a healthy individual an end-point nystagmus could occur, once the angle of eye deviation is greater than 40◦ . But preflight there was no gaze-evoked nystagmus in such ’extreme’ positions for all cosmonauts and its sudden appearance postflight should not be counted as a normal physiological reaction.

Before spaceflight, all cosmonauts but one had normal SpEM. This one cosmonaut developed a persistent spontaneous nystagmus in the central position in both horizontal and vertical planes (AN y = 2.5 ± 0.3◦ ; VN y =4.3 ± 0.8◦ *s−1 ; FN y = 0.5 ± 0.04 Hz). On R+1-2, 12 cosmonauts had normal SpEM and 7 cosmonauts had disturbed SpEM with an increased saccadic activity (square-wave jerks) and slow wave drifts. The remaining seven cosmonauts had spontaneous nystagmus (A N y = 3.5 ± 0.5◦ ; VN y = 6.1 ± 0.7 ◦ * s−1 ; F N y =1.5 Hz) and gaze evoked nystagmus (A N y = 2.5 ± 0.5◦ ; VN y = 3.9 ± 0.7 ◦ * s−1 ; F N y = 0.5± 0.08). Gaze evoked nystagmus was again observed in three cosmonauts on R+4-5. On R+8-9, six cosmonauts demonstrated increased squarewave jerks and slow wave drifts, whereas other cosmonauts regained normal SpEM. On R+13-14, SpEM had returned to normal for all cosmonauts.

Fixation Saccades (FS)

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Analysis of saccadic eye movements in horizontal and vertical planes on R+1-2, R+4-5, and R+8-9 has showed that the majority of cosmonauts required an increased number of corrective saccades to foviate the target (Fig. 1). This increase of corrective saccades as well as a significant decrease of amplitude and peak velocity of the primary saccade resulted in delay to acquire both horizontal and vertical stimuli by up to 2-3 times from the normal baseline time required for a target acquisition. Total reaction time was increased significantly until R+89, although latency differed significantly from the baseline only on R+1-2. Parameters of pre- and postflight FS are presented in Table I .

To emphasize effects of microgravity upon various parameters of saccades (amplitude ratio, peak velocity etc.), authors analyzed not only the actual parameters but also their differences in comparison with the baseline (i.e., samplings did not contain parameters per se, but the delta/difference between a parameter on postflight day and its baseline value). Both approaches for parameters themselves and for parametersâ&#x20AC;&#x2122; differences have shown identical results concerning significant changes postflight in comparison with the baseline. Cosmonauts demonstrated a statistically significant degradation of all parameters except latency until R+8-9. Postflight there was a significant increase in variation of corrective saccades (increased coefficient of variation) which can be caused by intragroup differences. Prior to spaceflight, 62% of cosmonauts had no corrective saccades and the remainder

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Special Edition on Sensorimotor Alterations Associated with Spaceflight had them in the range of 5 to 10%, but on R+1-2 and R+4-5 all cosmonauts without exception had increased numbers of corrective saccades between ≈ 20 - 35% for horizontal stimuli and ≈ 30 - 45% for vertical stimuli.

Smooth Pursuit (SP) Analysis of SP has shown not only disturbances in the pursuit function, but also a complete breakdown of the reflex which was observed in nine cosmonauts. These cosmonauts were unable to smoothly pursue either the linear or sinusoidal stimulus (or both stimuli) and unconsciously chose a new, saccadic strategy for the VT. This change is clearly revealed in Fig. 2 . A stepwise rather than smooth gaze motion (i.e., a sequence of corrective saccades) while tracking the sinusoidal and linear stimuli was enhanced on R+1-2 and R+4-5. Table II contains gain of the SP (gSP) pre- and postflight. gSP was analyzed by both repeated measures parametric ANOVA (F-test and post hoc analysis by Tukey’ s method) and nonparametric (Friedman’s test and post hoc pairwise comparisons made by Wilcoxon with a Bonferroni correction). Significant differences were revealed for horizontal gSP on R+4-5 and R+8-9.

During preflight velocity of the VT was practically equal to velocity of the stimulus (gSP ≈ 1.0). After spaceflight gSP was significantly decreased during the entire examination period. Despite the process of readaptation to terrestrial conditions (gSP was signifi cantly increased on R+4-5 and R+8-9 in comparison with the previous

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Special Edition on Sensorimotor Alterations Associated with Spaceflight day of examination), SP function had only partially recovered on R+8-9.

Gaze Holding (GH) on Real and Imaginary Targets Before spaceflight, cosmonauts were quite successful in their ability to hold their gaze on the imaginary target (last observed position of the stimulus). However, after spaceflight all GH parameters were significantly degraded and the success of the reaction was decreased. Parameters of the GH pre- and postflight are presented in Table III , and it is clearly evident that the reflex was not fully recovered even on R+8-9. Fig. 3 shows eccentric GH on real and imaginary targets in the horizontal and vertical plane preflight and on R+2. It should be noted that on R+1-2 gaze-evoked nystagmus was registered during the eccentric gaze on an imaginary target.

Static Torsional Otolith-Cervical-Ocular Reflex (OCOR) Preflight amplitude of the compensatory torsional ocular counter-rolling remained within the expected 4-8◦ normal range and the torsional reflex was symmetrical except for one cosmonaut. This cosmonaut had an asymmetrical reflex: his eyes counter-rolled by 4◦ during head tilt to the left shoulder and by 8◦ during head tilt to the right shoulder. Tests performed on R+1-2 did not produce torsional compensatory counter-rolling in four cosmonauts. A reversed reflex was registered in three cosmonauts (torsional counter-rolling took same direction as the head tilt), and the amplitude of OCOR was reduced by half in another seven cosmonauts. Several cosmonauts showed square wave jerks in the horizontal plane and an almost continuous upward beating nystagmus in the vertical plane. No changes were found in only three cosmonauts.

On R+4-5 and R+8-9 only six cosmonauts showed a decreased OCOR. For other cosmonauts the amplitude of torsional counter-rolling was either equal to or close to the baseline. Dynamics of these changes are shown in Table IV . Statistical analysis was made by ANOVA F-test and Friedman’s test. Both methods with a significance

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Special Edition on Sensorimotor Alterations Associated with Spaceflight level being α= 0.01 have shown that there were significant differences within the whole group both for head tilts rightward and leftward. Post hoc multiple comparisons with significance level α= 0.01 made by a parametric (Tukey’s test, Newman- Keuls’ and Dunnet’s tests) and nonparametric (Wilcoxon test with a Bonferroni correction) methods have shown similar results. For both directions of the head tilt, amplitudes of the OCOR on R+1-2 and R+4-5 were significantly decreased in comparison with the baseline and R+8-9, and also there was a significant difference between R+1-2 and R+4-5 for leftward head tilt. Amplitude of the OCOR reached its preflight level only on R+8-9. Gain of the OCOR was analyzed with α= 0.01 by the same methods as the amplitude mentioned above. This analysis has shown identical results and allows us to conclude that signifi cant changes in static torsional OCOR found postflight should not be explained by differences of the head tilt angle.

Dynamic Horizontal Vestibular-Cervical-Ocular Reflex (HVCOR) During Head Yaw Rotations with Eyes Closed Gain of the HVCOR (gHVCOR) before spaceflight was within the normal range of 0.4-0.5 in all cosmonauts. The gHVCOR analyzed pre- and postflight is presented in Table IV . After spaceflight cosmonauts were divided into three groups depending on a trend in gain values: 1) gHVCOR was increased; 2) gHVCOR was decreased; and

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Special Edition on Sensorimotor Alterations Associated with Spaceflight 3) there was no change in the gHVCOR. It was found that for the first two groups (with increased and decreased gain), postflight changes were significant and prolonged up to R+9.

Vestibular Reactivity (VR) During Head Yaw Rotations with Eyes Closed Before spaceflight active head yaw rotations produced a short-term nystagmus in only three cosmonauts. However on R+1-2, 19 cosmonauts demonstrated an increased VR. Of these 19 cosmonauts with an increased VR, 11 had a constant nystagmus (AN y ≈ 6-10◦ ; VN y ≈ 6-20◦ *s−1 ; FN y ≈ 2-4Hz). In another eight cosmonauts along with an increased VR there was a sharp decrease of compensatory eye movements during head yaw rotations, although nystagmus was observed throughout the test. For the remaining seven cosmonauts, VR did not change from the baseline values. VR preflight and on R+1-2 is shown in Fig. 4 . On R+4-5, seven cosmonauts maintained an increased VR, while for other cosmonauts it was returned to the baseline, and by R+8-9 VR was back to normal in all but one cosmonaut.

Characteristics of the vestibular-induced nystagmus are presented in Table IV . They were analyzed by parametric ANOVA (F-test + post hoc analysis by Tukey’s method). As mentioned earlier, there was almost no vestibular-induced nystagmus preflight and postflight on R+8-9, but on R+1-2 and R+4-5 nystagmus was clearly manifested and significantly increased in comparison with baseline and R+8-9. In addition to the variance analysis, we used Pearson’s and Spearman’s correlation criteria to detect the existence (or absence) of direct (linear) relationship between readaptation changes in individual’s levels of the vestibular system and various parameters of the VT (FS,SP, GH). In other words, for each parameter the sampling contained 3 slices (points): a subtraction (delta) between parameter’s value preflight and on R+1-2, a subtraction between values on R+1-2 and R+4-5, and a subtraction between values on R+4-5 and R+8-9.

Analysis of correlation between postflight changes in OCOR and VR showed a significant negative correlation (r = -0.76, P < 0.05) on R+1-2. On R+4-5 it was increased up to r = -0.44 and remained practically unchanged on R+8-9 (r = -0.42). The most marked correlation was the one between amplitude of OCOR and FS amplitude ratio (r = 0.7 ... 0.9, P <0.05) and peak velocity (r = 0.7 ... 0.95, P < 0.05). This correlation between OCOR and FS was strong during the whole readaptation period both for horizontal and vertical saccades. Along with the vestibular system, central structures of the CNS (SpEM) were also correlated with visual tracking. Both postflight changes in smooth pursuit (SpEM/gSP r ≈ -0.6) and fixation saccades (SpEM/ amplitude ratio ≈ 0.7; SpEM/peak velocity ≈ 0.8; SpEM/ corrective saccades ≈ -0.8) were correlated with SpEM on R+1-2 and

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Special Edition on Sensorimotor Alterations Associated with Spaceflight R+4-5. However, it concerned only VT in the horizontal plane and there was no correlation between SEM and any parameter of the vertical VT. Results shown in this work demonstrate that most parameters, which characterize the state of the vestibular and oculomotor function during readaptation to terrestrial gravity, undergo significant changes in comparison to the baseline. As authors are continuing to observe, unique methods or strategies for gravitational compensation are adopted by individual astronauts and cosmonauts . For the most part authors believe that earlier data as well as data presented in this paper, show that these strategies are not conscious decisions; rather they represent the way that an individual’s CNS adapts to changes that affect performance and function. Along with unique adaptive changes to the novel gravitational environment, authors were able to find regular, typical consistent changes that appeared across individuals. The postflight increase in SpEM, degradation of the GH ability, and the new saccadic tracking strategy instead of the SP indicate the involvement of central mechanisms of the vestibular system and reflect, probably, changes in functioning of the vestibular nuclei, reticular formation of the middle brain, and the cerebellum .

Torsional ocular counter-rolling induced by a body or head tilt was examined after spaceflight as an indicator of the adaptation of otoliths to microgravity. In microgravity there is no otolith-induced compensatory torsional ocular counter-rolling in response to a sustained tilt . Previously it was shown that torsional ocular counterrolling was reduced both after short-duration and long-duration missions . Similar changes were observed in two primates after spaceflight. However, there was no change in torsional ocular counter-rolling in astronauts who flew in the 1998 Neurolab Mission (STS-90) . In this experiment four crewmembers were examined pre-, in-, and postfl ight. Astronauts were exposed to artifi cial gravity (1 g or 0.5 g centripetal acceleration) generated by centrifugation. Absence of differences between pre-,in-, and postfl ight torsional ocular counter-rolling could be explained by an intermittent exposure to artificial gravity during the 16-d mission, which had prevented deconditioning of otolith-ocular reflexes in microgravity. These data allow us to consider in-flight centrifugation as a countermeasure for vestibular disorders occurring during and after spaceflight. Postflight data (absence, inversion, or a sharp decrease of the OCOR) show that adaptation to microgravity is associated with a deep and long suppression of OCOR. Rapid adaptation of multisensory integration in vestibular pathways When an astronaut transitions to microgravity or returns to earth, the vestibular input arising from self-motion will not match the brain’s expectation. This neurophysiological studies have provided insight into how the nervous system rapidly reorganizes when vestibular input becomes unreliable by both (1) updating its internal model of the sensory consequences of motion and (2) up-weighting more reliable extra-vestibular information.

These neural strategies, in turn, are linked to improvements in sensorimotor performance (e.g., gaze and postural stability, locomotion, orienting) and perception characterized by similar time courses.

During space exploration missions, however, gravity becomes minimal resulting in a mismatch between the brain’s expectation of sensory consequence of movement and that actually experienced. This has important implications for astronauts. Specifically, astronauts show impaired balance, locomotion, gaze control, dynamic visual acuity, eye-head-hand coordination during the space flight. The effects of this decrease in gravity are most pronounced immediately after the transition to microgravity . When moving, astronauts not only experience impairments in sensorimotor performance but also report spatial disorientation and destabilizing sensations such as the feeling of have suddenly turned upside-down and/or difficulty in sensing the location of their own arms and legs .

It is generally thought that these symptoms arise because the integration of sensory input from the vestibular system with that from the proprioceptive, somatosensory, and visual systems mis-informs the brain relative to its existing (i.e., earth-based) "internal" model of the expected sensory consequences of motion . This conflict between the brain’s expectation of sensory feedback and the actual sensory feedback experience in microgravity is also thought to be the cause of space motion sickness experiences during the initial stages of space flight .

Overall, nearly 70% of all astronauts experience impaired motor performance and/or space motion sickness .

To develop new training and treatment approaches, it is important to understand the mechanisms that underlie these symptoms as well as those that are responsible for recovery.

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Neural Correlates of Sensorimotor Adaptation: Sensory Conflict In single unit recording studies authors have shown that a subclass of neurons in the vestibular nuclei, which project to the spinal cord and to vestibular thalamus, respond preferentially to passive head movements. For example, during everyday activities, the otoliths are activated both by gravity and by our own self-motion . In response to active motion, the otolith afferents in the 8th nerve send robust signals to the vestibular nuclei .

However, at the next stage of processing, this "reafferent" sensory input is canceled .

This recent work further suggests that this cancelation is mediated by a mechanism that compares the expected consequences of self-generated movement (computed by an internal model located in the cerebellum) and the actual sensory feedback (Figure 1A). Notably, the un-canceled sensory input ("exafference") resulting from passive movement is thought to allow the brain to compensate for unexpected postural disturbances and ensure perceptual stability . Such a mechanism is similarly consistent with the observation that impairments in balance, locomotion, gaze control, dynamic visual acuity, eye-head-hand coordination and perception are most serious during the initial phase of space flight and re-entry. Once the brainâ&#x20AC;&#x2122;s internal model had been updated

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Special Edition on Sensorimotor Alterations Associated with Spaceflight to account for the change in the forces gravity, it learns to expect a different pattern of input from the 8th nerve during motion that again ensures accurate motor control and perceptual stability.

Neural Correlates of Sensorimotor Adaptation: Dynamic Re-Weighting of Multimodal Inputs The symptoms of space motion sickness/spatial disorientation can initially be quite debilitating, they decrease over time (from 1 h to 4 days) such that astronauts are able to comfortably make voluntary head movements during a mission. Astronauts again experience these symptoms upon returning to Earthâ&#x20AC;&#x2122;s 1-g environment.

Because access to astronauts is more straightforward in this latter condition, it is more often the focus of quantitative studies.

Interestingly, aspects of the motor performance observed after returning to 1-g environment astronauts are similar to those observed in the patients from acute unilateral vestibular peripheral loss. In both conditions, the actual vestibular feedback experienced during self-motion is initially different from that which is expected.

Recent studies in laboratory have provided insights into the neural mechanisms that underlie the adaptation of the sensorimotor integration following peripheral vestibular loss .

In particular, authors discovered that compensation is mediated by the dynamic reweighting of inputs from different modalities (i.e., extravestibular versus vestibular) at the level of the single neurons that constitute the first central stage of vestibular processing. At least two types of extravestibular inputs can substitute for the lost vestibular input, (1) proprioception and (2) motor efference copy signals.

As reviewed above, in normal conditions, vestibular responses to active motion are suppressed when there is a match between the brainâ&#x20AC;&#x2122;s estimate of proprioceptive feedback and the actual sensory feedback. However, under normal conditions (1) passive stimulation of neck proprioceptors in isolation does not alter neuronal responses and (2) the generation of motor efference copy signals does not alter neuronal responses when the head is prevented from moving (i.e., in this condition there is a mismatch between expected and actual feedback).

In contrast, following peripheral vestibular loss, neurons respond differently. First, robust response to passive stimulation of neck proprio-ceptors are rapidly unmasked in the early vestibular pathway (Figure 1B, top panel, red trace), can be linked to the compensation process as evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons .Furthermore, when the head is restrained neuronal responses to motor efference copy are unmasked over the course of weeks (Figure 1B, top panel, purple trace).

The Dynamics of Behavioral Adaptation: Vestibular Compensation and Re-Entry The time course of the dynamic re-weighting of multimodal information observed at the level of single neurons, follows a similar time course to the improvement observed in (1) patient performance following vestibular loss and (2) astronaut return back to earth (Figure 1B, compare top and middle panels). First, patients generally show significant improvement in postural performance in first days after lesion, with more gradual improvement seen within a 1-2 weeks (Figure 1B, middle panel, gray trace ). Early sensorimotor symptoms include significant head tilt in the roll plane toward the lesion and a tendency to deviate toward the lesioned side when walking .

Second and similarly, astronauts show rapid sensorimotor learning in the first day after return, with more gradual improvement in the following weeks ultimately returning performance to pre-flight levels. Superimposed in Figure 1B (middle panel) for comparison is an example of the adaption that occurs following return from space flight (e.g., locomotor performance). A similar time course has been reported for balance control recovery , as well as perception, spatial orientation, eye-head and head-trunk coordination following re-entry.

Neural Correlates of Perception: Dynamic Re-Weighting of Multimodal Inputs Authors have further demonstrated that, following partial vestibular loss, neurons at the first central stage of vestibular processing, in the vestibular nuclei, show increased variability in response to vestibular stimulation.

This increase in variability does not improve over time and ultimately constrains neural detection thresholds (Figure 1B, bottom panel, blue trace). As noted above, these neurons not only contribute to posture and balance via projections to the spinal cord, but also send information to the thalamus, and then on to regions of cerebral cortex. Accordingly, they likely make a vital contribution to the perception of spatial orientation and self-motion . This then raises the question: What mechanisms underlie the observed improvements in perceptual threshold? Indeed, authors found that sensory substitution with extravestibular (i.e., proprioceptive; Figure 1B, bottom panel, red trace) inputs provides a neural substrate for improvements in self-motion perception following vestibular loss which similarly shows significant improvement over this same time frame.

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D ID YOU KNOW ?

E PWORTH S LEEPINESS S CALE (ESS) The ESS is a standardized and validated questionnaire assessing the likelihood that the participant will fall asleep during certain activities (Johns 1991). The ESS consists of 8 questions that describe daily situations that can induce sleepiness. Each question is graded from score 0 ("not likely to fall asleep") to score 3 ("very likely to fall asleep"). The ESS score ranges from 0 (minimum) to 24 (maximum). A score of 10 is used as a cut-off value to make a distinction between normal individuals (ESS ≤ 10) and individuals suffering from excessive daytime sleepiness (ESS > 10). The ESS was incorporated to assess the typical fatigue and drowsiness associated with sopite syndrome and was filled in twice by each participant: prior to and immediately after the parabolic flight.

How Sleepy Are You? How likely are you to doze off or fall asleep in the following situations? You should rate your chances of dozing off, not just feeling tired. Even if you have not done some of these things recently try to determine how they would have affected you. For each situation, decide whether or not you would have: • No chance of dozing = 0 • Slight chance of dozing = 1 • Moderate chance of dozing = 2 • High chance of dozing = 3

Reference:

R

Dr Murray Johns, The Epworth Sleepiness Scale, Website . (http://epworthsleepinessscale.com/about-epworthsleepiness/)

Special Edition on Sensorimotor Alterations Associated with Spaceflight

Tolerance to Extended Galvanic Vestibular Stimulation: Optimal Exposure for Astronaut Training Authors have developed an analogue of postflight sensorimotor dysfunction in astronauts using pseudorandom galvanic vestibular stimulation (GVS). To date there has been no study of the effects of extended GVS on human subjects and our aim was to determine optimal exposure for astronaut training based on tolerance to intermittent and continuous galvanic stimulation. We have developed a technique to replicate the postflight sensorimotor experience of astronauts by disrupting vestibular input in normal subjects by passing small electrical currents between mastoidal surface electrodes (bilateral bipolar galvanic vestibular stimulation - GVS).

The pseudorandom current waveform, a sum of sines with dominant frequencies at 0.16, 0.33, 0.43, and 0.61 Hz, was derived in a preliminary study (N = 4) comparing anterioposterior sway in normal subjects undergoing GVS during computerized dynamic posturography with postflight astronaut performance on the same device.

Authors speculated that postflight postural deficits were the result of changes in central processing of lowfrequency otolith information during flight and that modulating otolithic afferent input to the cerebellum with a pseudorandom current waveform may produce similar imbalance. When subsequently applied to a group of healthy subjects (N = 20), the GVS analogue accurately replicated the postural instability , locomotor impairment, and reduced dynamic visual acuity observed in astronauts after return from shuttle and International Space Station missions. In addition, a study of pilot performance during simulated shuttle landings in the VMS demonstrated that GVS degraded spatial orientation and fine motor control, inducing ’hard’ landings (touchdown speed above target) consistent with that observed in actual shuttle landings. Subjective validation was provided by seven veteran astronauts (five shuttle, one ISS, one Skylab), who reported that the motor effects and illusory sensations of movement generated by the GVS analogue were remarkably similar to their postlanding experience . The ability of GVS to accurately replicate the postural, locomotor, oculomotor, and perceptual difficulties experienced by astronauts suggests a vestibular basis for these postflight sensorimotor deficits.

A total of 60 participants were randomly assigned into 2 groups: 3.5 mA [ N 5 30; 17 men, 13 women; mean age 30.3 yr (95% CI 10.8)] and 5 mA [ N 5 30; 15 men, 15 women; age 28.7 yr (CI 10.3)] peak GVS current.

Subjects had no prior experience with GVS. Mount Sinai School of Medicine’s Institutional Review Board approved the experiments and subjects gave their informed consent and were free to withdraw at any time.

Results Intermittent Exposure GVS was well tolerated at both the 3.5-mA and 5-mA levels of exposure. At 3.5 mA the average time of exposure was 10.5 min and 93.3% (28/30) of the subjects completed the experiment ( Table I ). The majority of subjects (25/30) reported no ( N = 18) or at most mild ( N = 7) motion sickness symptoms (nausea, dizziness, drowsiness, cold sweat, pallor) and 3 subjects reported moderate symptoms (nausea, dizziness, cold sweat, pallor).

Two subjects (one man and one woman) asked to interrupt the experiment due to severe nausea following a mean GVS exposure of 3.4 min. In post-GVS testing two subjects reported mild symptoms (nausea, dizziness).

None of the subjects experienced headache or flushing. At 5 mA peak current, 90% (27/30) of the subjects completed the experiment with an average of 10.5 min GVS exposure, with 22 subjects reporting no ( N = 20) or at most mild ( N = 2) symptoms (nausea, dizziness, headache). Five subjects reported moderate symptoms (nausea, dizziness, flushing, pallor, cold sweat) and three female subjects asked to interrupt the experiment due to severe nausea following a mean GVS exposure of 5.5 min. No symptoms were reported in post-GVS testing.

Thus, out of the 60 subjects exposed to a cumulative 10.5 min of intermittent GVS, 47 (78.3%) reported no or at most mild motion sickness symptoms, 8 (13.3%) reported moderate symptoms, and 5 subjects (8.3%) experienced severe nausea and did not complete the experiment (Table I).

The MSSQ was not a good predictor of motion sickness susceptibility to intermittent GVS. The MSSQ of the 5 subjects who experienced severe nausea [31.8 (CI 9.4); range 18.5 - 44.9] did not differ significantly (ANOVA; P = 0.2) from the MSSQ of all 60 subjects [18.8 (CI 4.63)]. Moreover, significant motion sickness symptoms ˝ 85.4]. were not reported by 22 subjects with above-average MSSQ scores [35.4 (CI 6.9); range 19 U Continuous Exposure Continuous GVS was better tolerated by the 3.5-mA group [MSSQ 11.2 (CI 7.2)] than the 5-mA group [MSSQ 12.2 (CI 8.8)]. In the 3.5-mA group, all 12 subjects completed 20 min of continuous GVS exposure; 11 subjects reported no motion sickness symptoms at all, with only 1 subject (female) reporting mild dizziness. At 5 mA, 75% of the subjects (9/12) completed the 20-min exposure. Of these nine subjects, seven reported no motion sickness symptoms, one (male) reported mild nausea, dizziness, and cold sweat, and one (male) reported moderate dizziness and severe nausea immediately after completion of the 20-min exposure. Three subjects [1 man, 2 women; MSSQ average 32.2 (CI 23.4)] requested early termination of GVS after a mean exposure of 9.8 min due to severe nausea. No motion sickness symptoms were reported by any of the 24 subjects 15 min after GVS

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Special Edition on Sensorimotor Alterations Associated with Spaceflight exposure. No motion sickness symptoms were reported pre-GVS and headache, pallor, or drowsiness were not reported at any stage. Thus, out of the 24 subjects exposed to 20-min continuous GVS, 20 (83.3%) reported no or at most mild motion sickness symptoms. Four subjects (16.7%) experienced severe nausea at 5 mA peak current, three of whom terminated exposure early; these four subjects subsequently completed a total of 20 min intermittent 5-mA GVS (10 sessions of 2 min each, with a 1-min break between applications) without reporting any motion sickness symptoms whatsoever. The MSSQ of all 24 subjects [11.7 (CI 7.9); range 0 - 55.4] was not significantly different (ANOVA P = 0.06) to the MSSQ scores of the four subjects who reported severe nausea [27.5 (CI 18.9); range 13.6 - 55.4]. Five subjects who did not report any motion sickness symptoms had MSSQ scores [24.6 (CI 5.4); range 18.5 - 34.3] above the group mean.

The results of this study demonstrate that extended exposure to GVS is well tolerated at current amplitudes of up to 5 mA. During intermittent GVS, the large majority of subjects (91.7%) had little difficulty completing the 10.5-min exposure and there was no obvious effect of current amplitude (3.5 or 5 mA) on the incidence of motion sickness reports. Thus, in the general population we would predict less than 9% of subjects to be intolerant of intermittent GVS at amplitudes up to 5 mA. For the continuous study authors selected from the 78% of subjects who experienced none or at most mild symptoms during intermittent GVS, a group we would expect to be roughly equivalent to the astronaut population in terms of motion sickness insusceptibility. During 20-min continuous galvanic stimulation there was an effect of current amplitude, with almost no motion sickness reported at 3.5mA (one subject reporting mild dizziness), but a third of subjects at 5 mA peak current (4/12) experienced severe nausea, three of whom requested early termination of the stimulus.

However, it was the temporal nature of GVS delivery that appeared to be the critical factor in the development of motion sickness symptoms, rather than the total duration of exposure; the four subjects reporting severe nausea during 20-min continuous 5-mA GVS completed a total of 20 min intermittent 5-mA stimulation (10 3 2-min epochs) without any motion sickness whatsoever.

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