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Review of NASA’s Biomedical Research Program 2 Sensorimotor Integration INTRODUCTION Sensorimotor integration plays a critical role in the control of posture and movements, and so is essential for locomotion and using tools. On exposure to an altered gravitational environment, there are changes in the sensory signals originating from the vestibular system, particularly those coming from the otolith organs. These changes have major effects on visual and spatial orientation, and on mobility during spaceflight and on return to Earth. Disturbances occur more frequently on longer-duration missions, and complete recovery can take weeks and, in some cases, months. Disorientation, impaired visual acuity, and postural instability can have profound effects on the performance of sensorimotor tasks, including piloting the spacecraft or making an emergency egress. Accordingly, ground-based research studies funded by the National Aeronautics and Space Administration (NASA) have focused on examining the time course of adaptation of the gravity-sensitive properties of the vestibulo-ocular, vestibulo-collic, and vestibulo-spinal reflexes and on determining how vestibular, proprioceptive, and visual information is used to control head and trunk position, maintain postural stability, and assist in locomotion. In addition to studying these activities in normal subjects, research is also performed on subjects with pathological changes in the neurovestibular system, as symptoms in these latter cases often mimic the changes observed in astronauts during and after spaceflight. Early in-flight performance for many astronauts is often marked by space motion sickness, particularly for astronauts with no previous spaceflight experience. In long-duration flights, space motion sickness can also be triggered by illusions of visual reorientation that occur when astronauts misperceive their orientation with respect to the environment. The chapter “Sensorimotor Integration” in the Strategy report (NRC, 1998) defines six priority areas of investigation: (a) spatial orientation; (b) posture and locomotion; (c) vestibulo-ocular reflexes (VORs) and oculomotor control; (d) space motion sickness; (e) central nervous system (CNS) reorganization and vestibular processing during microgravity; and (f) teleoperation. In addition, the chapter “Developmental Biology” in that report contained three sections pertinent to sensorimotor integration: (a) development of the vestibular system; (b) neural space maps; and (c) neuroplasticity. Grants focused on these last
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Review of NASA’s Biomedical Research Program three topics are funded primarily through the Gravitational Biology and Ecology (GB&E)1 program and have been included in this review. The current NASA biomedical research program is considered in light of all nine subdiscipline areas. Research projects that have a primary focus on the interactions of the vestibular system with the cardiovascular or musculoskeletal systems are not covered here. NASA’S CURRENT RESEARCH PROGRAM IN SENSORIMOTOR INTEGRATION Altogether in FY 1999, NASA funded 39 projects relevant to sensorimotor integration; these are classified in Table 2.1 according to the nine subdiscipline areas described above. Funding for this research was contributed by three NASA programs (Biomedical Research and Countermeasures, Advanced Human Support Technologies, and Gravitational Biology and Ecology), the National Space Biomedical Research Institute (NSBRI), and a new cooperative National Institutes of Health (NIH)-NSBRI program. Within the Biomedical Research and Countermeasures (BR&C) program, sensorimotor integration research is included in three disciplines: (1) behavior and performance; (2) physiology: neuro-science; and (3) operational and clinical. The 12 projects funded through the GB&E program are concerned with the basic mechanisms underlying vestibular function or the effects of gravity on vestibular development. In FY 1999, the total funding for research on sensorimotor integration was approximately $7.8 million, which places this work in the top quarter of NASA’s Biomedical Research (NASA, 1999). In FY 1998, the funding level for sensorimotor integration research was approximately $6 million, with 40 projects being supported. The increase in funding in FY 1999 reflected the new cooperative NIH-NSBRI program for the support of vestibular research, which had a funding level of $1.4 million, 80 percent of which was provided by the National Institute of Deafness and Communicative Disorders. Studies on sensorimotor integration are carried out in all four components of the NASA life sciences research enterprise, including the laboratories at Johnson Space Center (JSC), Ames Research Center (ARC), and numerous universities funded either through the NASA Research Announcement (NRA) mechanism or through the NSBRI. In addition to conducting intramural research, scientists at JSC and ARC routinely collaborate on university-based research programs. JSC scientists have also been involved in setting up laboratories in Star City, Russia, to investigate postural control, locomotion, and visual target acquisition after long-duration spaceflight. The Neurological Function Section at JSC is focused on human studies of posture and locomotion, vestibulo-ocular reflex and oculomotor control, and visual adaptation and space motion sickness. Specialized facilities exist for pre- and postflight studies of visuospatial adaptation and postural stability. At ARC, both human and animal studies are conducted on spatial orientation, vestibulo-ocular reflexes and oculomotor control, and space motion sickness. ARC has facilities for centrifuge studies on humans to determine the time course of adaptation to different g-levels and the effects of altered gravity on human behavior and performance. The center also has several facilities for testing the responses of the vestibular system to linear and angular acceleration in small animals and in human subjects. There are three major research projects supported entirely by the NSBRI in the area of neuro-vestibular adaptation, two of which have a coinvestigator at JSC. These are focused on adaptation of vestibular reflexes to different gravitoinertial force conditions; spatial orientation and mobility, in particular visually induced tilt and reorientation illusions; and eye, head, and body movements during locomotion and their stability in a range of environments. A fourth project on neurovestibular adaptation 1 Recently retitled the Fundamental Biology Research Program (FBRP).
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Review of NASA’s Biomedical Research Program TABLE 2.1 Summary of Funding in FY 1999 for Sensorimotor Integration Subdisciplines NRA NSBRI NSBRI-NIH Subdiscipline Total ($ thousands) No. of Projects Total ($ thousands) No. of Projects Total ($ thousands) No. of Projects Spatial orientation 1,188 5 339 1 112 1 Posture and locomotion 1,024 5 369 1 0 0 VOR and oculomotor control 962 6 321 1 1,301 5 Space motion sickness 130 1 0 0 0 0 CNS reorganization and vestibular processing during microgravity 555 3 0 0 0 0 Teleoperation 179 1 0 0 0 0 Development of vestibular system 706 6 0 0 0 0 Neural space maps 84 1 0 0 0 0 Neuroplasticity 514 2 0 0 0 0 Total 5,342 30 1,029 3 1,413 6 supported by the NSBRI is an interdisciplinary proposal (i.e., identified as a synergy project) concerned with the visual and vestibular autonomic influence on short-term cardiovascular regulatory mechanisms. In the BR&C program, research on sensorimotor integration is heavily concentrated on human studies of postural stability, the vestibulo-ocular reflex and oculomotor control, and visuospatial orientation and adaptation. One-third (6/18) of the projects in the BR&C program are focused on postural control and motor adaptation to variations in gravitational force level, one of the issues identified in the Strategy report. The other two recommendations made in the Strategy report for future studies of posture and locomotion concern the development of ancillary sensory aids to facilitate postural and locomotory control and to assist in adaptation during transitions between gravitational force environments, and the development of animal models of reentry disturbances. These do not appear to be the primary focus of any studies being funded by NASA at present. Studies of oculomotor control and vestibular reflexes account for approximately one-third of the sensorimotor integration projects funded through NASA’s BR&C program and represent a major emphasis of the program. These projects address all of the issues raised with respect to this area in the Strategy report. This research has contributed to the understanding of the effects of microgravity on the vestibulo-ocular system, on the control of head and eye position, and on how the vestibular reflexes adapt to altered gravitational conditions. Accurate spatial orientation is essential in order to control one’s movements and to interact with objects in the environment. On Earth, gravity plays a fundamental role in spatial orientation. In the absence of gravitational cues during spaceflight, astronauts often misinterpret visual information and experience visual reorientation illusions when they misperceive their own orientation with respect to the
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Review of NASA’s Biomedical Research Program environment. Six projects in the BR&C program are concerned with spatial orientation, which is often studied in conjunction with gaze stability or postural and locomotor control. This research includes both flight- and ground-based studies and is consistent with most of the recommendations made for research on spatial orientation in the Strategy report. In particular, there are human studies on the identification of sensory, motor, and cognitive factors that influence the ability to adapt to different gravitational environments, as well as animal research on the neural coding of spatial mobility. One recommendation concerning the influence of microgravity on the integrative coordination of active movements before, during, and after spaceflight does not appear to be the subject of study at this time. Space motion sickness can be an operational problem during the first 72 hours of flight and can be controlled with intramuscular injections of promethazine. It can also be triggered during spaceflight by visual reorientation illusions, which occur when crew members misinterpret visual cues from surrounding objects, usually when they are working in an unfamiliar “agravic” orientation. Only one project specifically devoted to space motion sickness is funded through NASA’s BR&C program, and it is concerned with the effects of promethazine on human performance. There are a few structural and functional studies on the interactions between the vestibular system and autonomic function, including cardiovascular regulation, which address one of the four recommendations made for space motion sickness in the Strategy report. Another project examines the possibility of maintaining dual adaptations to more than one force background, a subject recommended for study in the Strategy report. Other recommendations made in the Strategy report, including studies of the relation between motion sickness and altered sensorimotor control of the head and body; the time course of the Sopite syndrome (i.e., a form of motion sickness associated with prolonged exposure to unusual gravity conditions, whose primary features include drowsiness, fatigue, lack of initiative, apathy, and irritability); and the relation between terrestrial and space motion sickness have not yet been investigated. Studies on vestibular signal processing and development funded through the GB&E program (n = 12) represent approximately one-third of the total number of research projects included in the topic of sensorimotor integration. The research is focused on measuring the changes in signal processing by peripheral vestibular afferents in altered gravitational environments and on the effects of gravity on vestibular development using a wide range of animal models (see discussion of validation of animal models below). The research is focused primarily on structure-function studies of the peripheral vestibular system. Findings on the central vestibular system are lacking so far, although they are cited in a presently funded proposal. With respect to the recommendations made in the Strategy report, as yet there are no studies focused on the development of the central vestibular system or on how exposure to microgravity affects neuroplasticity and the different space maps located in the brainstem, sensory and motor cortices, and corpus striatum. The Strategy report made two recommendations concerning studies of vestibular processing: (1) study the effect of altered calcium regulation in microgravity on otoconial development and regeneration in animal models and (2) perform in-flight electrophysiological recordings from otolith afferents and efferents, and investigate signal processing within the central vestibular pathways in animals. During the recent Neurolab flight, some studies were conducted on otoconial development in microgravity and preliminary electrophysiological recordings of otolith afferents were performed in fish. Consistent with the recommendations made in the Strategy report, research in the Biomedical Research and Countermeasures program is focused heavily on human studies, both flight and ground based, of postural stability, the vestibulo-ocular reflex and oculomotor control, and visuospatial orientation and adaptation. Studies of vestibular signal processing and development constitute about one-third of the total number of research projects included in sensorimotor integration research and are performed on a wide range of animal models. In keeping with the
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Review of NASA’s Biomedical Research Program recommendations of the Strategy report, this work is concerned with investigating signal processing by peripheral vestibular afferents in altered gravitational environments and the effects of gravity on vestibular development. However, other recommendations regarding the development of the central vestibular system and how exposure to microgravity affects neuroplasticity and neural space maps are not being adequately addressed at present. PROGRAMMATIC BALANCE Balance of Subdiscipline Areas NASA’s program of research on sensorimotor integration places a major and appropriate emphasis on characterizing the vestibular-related disturbances in visual and spatial orientation and posture observed in astronauts during and after spaceflight. Much of this work is performed on normal human subjects. Structure-function studies of the peripheral vestibular system represent a small but active component of the research supported by NASA on sensorimotor integration. Other areas, such as CNS reorganization and teleoperation, have not received adequate attention to date. Balance of Ground and Flight Investigations The total number of sensorimotor integration-related projects (39) is almost evenly divided between ground and flight research, which is appropriate. In FY 1999, the Advanced Human Support Technologies program (n = 3) funded only flight-based projects, whereas the Biomedical Research and Countermeasures program (n = 18) supported 7 flight and 11 ground-based studies and the Gravitational Biology and Ecology Program (n = 12) supported 5 ground-based and 7 flight projects (NASA headquarters). These 7 flight projects were primarily a continuation of Neurolab experiments or the analyses of data collected during that mission. Despite the paucity of flight opportunities due to the construction of the ISS, there are several funded projects that will be flight-borne when feasible. Emphasis Given to Fundamental Mechanisms There is an active research program directed toward elucidating the fundamental mechanisms underlying the function of the vestibular system. As yet, the human and animal studies are not well integrated, and findings from human research do not lead naturally to further exploration of fundamental mechanisms in experimental animal models or vice versa. Specifically, the findings from studies on basic mechanisms are not applied to derive new countermeasures that could improve astronauts’ performance and/or safeguard their health. Utilization and Validation of Animal Models Excluding the Neurolab projects, animal research receives less than 25 percent of the funds allocated for studies on sensorimotor integration and thus constitutes a relatively small but significant part of NASA’s biomedical research program. The research projects involving experimental animals are predominantly ground based and are performed mainly in university laboratories. This research is focused on the effects of gravity on signal processing and adaptation in the peripheral vestibular system and vestibular development using a wide spectrum of species including primates, rodents, birds, amphibians, fish, and mollusks. There are no animal studies on vestibular compensation in microgravity.
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Review of NASA’s Biomedical Research Program Although studies of vestibulo-oculomotor learning are being carried out on human subjects, no animal models have been investigated. NASA’s program of research on sensorimotor integration places a major and appropriate emphasis on characterizing the vestibular–related disturbances in visual and spatial orientation and posture observed in astronauts during and after spaceflight. These projects are almost evenly divided between ground and flight research, which is reasonable. Other areas identified in the Strategy report such as CNS reorganization and teleoperation have not received adequate attention to date. Although sensorimotor integration studies are focused heavily on human subjects, there is an active animal research program directed toward elucidating the fundamental mechanisms underlying the function and dysfunction of the vestibular system. As yet, human and animal studies are not well integrated with regard to understanding basic mechanisms underlying vestibular adaptation. DEVELOPMENT AND VALIDATION OF COUNTERMEASURES Countermeasures considered effective for some of the sensorimotor alterations that occur due to spaceflight include the administration of promethazine, crew training, time-line adjustments (i.e., not scheduling certain activities such as extravehicular activities (EVAs) during the first few days of spaceflight), timing of training with respect to the mission start, in-flight exercise, and assisted egress (NASA, 1997). Promethazine, an antimotion sickness drug, has been the treatment of choice in the Space Shuttle program for many years, although it does induce adverse side effects on human performance when tested on the ground (Harm et al., 1999). As yet, there are no systematic studies of the effects of promethazine on human performance in space, although one project has been funded. Most of the data regarding the lack of sedative side effects in space are anecdotal. Other pharmacologic treatments for motion sickness (e.g., selective muscarinic antagonists) warrant investigation as prophylactic treatment for space motion sickness. Clearly, training and exposure to altered gravitational environments, either on Earth or during previous missions, assist astronauts in adapting to spaceflight. These factors are cited as effective countermeasures (NASA, 1997). At present, it is unclear what specific aspects of this training facilitate adaptation or compensation. An essential prerequisite for developing virtual reality simulators is to identify which elements of the astronaut’s training facilitate adaptation to an altered gravitational environment and maintenance of spatial orientation in a spacecraft. There is evidence that previous spaceflight experience or repeated exposure to altered gravitational environments reduces the frequency of space motion sickness, spatial orientation problems, and disequilibrium. However, it is unknown whether this is accomplished in increments or whether steady state is achieved after a certain number of exposures. Centripetal acceleration induced by centrifugation has been proposed as an in-flight sensorimotor countermeasure to promote appropriate responses to sustained changes in gravitoinertial forces. Several research studies have been conducted with human subjects at JSC, ARC, and university laboratories to study the mechanisms of adaptation to altered gravitational environments and to examine postural stability following centrifugation. The ongoing exploration of artificial gravity as a possible countermeasure for sensorimotor impairment merits continued attention. However, the benefits derived by other systems (e.g., musculoskeletal) from exposure to artificial gravity may be limited ultimately by the adaptive capabilities of the vestibular system. It is not clear whether humans can maintain dual adaptations to different gravitational environments, although this is being studied at present. Human mobility in the spacecraft has not been studied in microgravity. Anecdotal reports suggest
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Review of NASA’s Biomedical Research Program that astronauts’ experiences in mock-ups, parabolic flights, neutral buoyancy, and virtual reality simulators assist them in orientation and mobility, but these have not been studied systematically to determine their effectiveness as countermeasures. Clearly, considerable individual differences exist in the ability to orient and navigate and to remain oriented using visual cues. There exists a substantial body of operational and experimental data on orientation, mobility, and postural control at JSC that has not been analyzed fully. These data could provide answers to some of the questions raised here. The individual variability in response to spaceflight makes it imperative to use as large a sample size as possible and a longitudinal design. Countermeasures that have been implemented to deal with the sensorimotor alterations that occur due to spaceflight include providing anti-motion sickness drugs and modifying the duration and timing of crew training. There is evidence that previous spaceflight experience or repeated exposure to altered gravitational environments reduces the frequency of space motion sickness, spatial orientation problems, and disequilibrium. However, it is unclear what specific pharmacological countermeasures or aspects of training promote adaptation to or compensation for altered gravitational environments. EPIDEMIOLOGY AND MONITORING At present, much of the information available on the frequency and severity of problems affecting the visual-vestibular and postural control systems during and after spaceflight is anecdotal or not accessible. However, data on the in-flight use of medications and on the incidence of space motion sickness have been collected as part of the Longitudinal Study of Astronaut Health. Data on the use of anti-motion sickness medications will continue to be collected since the International Space Station (ISS) Medical Operations Requirements Document (MORD) requires the operational monitoring of countermeasures, such as pharmacological preparations. In addition, the Integrated Testing Regimen (ITR), a standardized set of physiological and psychological tests that will be conducted before, during, and after spaceflight to examine countermeasure efficacy (NASA, 1999), includes a locomotor control test, a gaze holding test, and a functional neurological assessment. The Neurological Function Section at JSC is focused on human studies of sensorimotor integration and has established specialized facilities for pre- and postflight testing of visuospatial adaptation and postural stability. However, it lacks a formal program to measure the performance of astronauts over a prolonged period of time after flight using a variety of visual, spatial, and postural tasks. This type of study would provide information on how rapidly the visual-vestibular and postural control systems readjust to the gravitational environment on Earth and to what extent, and under what conditions, this readjustment may be incomplete. Much of the available information on the frequency and severity of problems affecting the visual-vestibular and postural control systems during and after spaceflight is anecdotal or not accessible. It is expected that the Integrated Testing Regimen will include a formal evaluation of the visual and postural control systems that will provide information on the efficacy of countermeasures. SUPPORT OF ADVANCED TECHNOLOGIES The final two priority areas of study identified in the Strategy report are central nervous system reorganization and teleoperation and telepresence. That report identified a need for preliminary studies using functional magnetic resonance imaging (fMRI) pre- and postflight to determine the effects of microgravity on sensory and motor cortical maps, and recommended that strategies be developed to
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Review of NASA’s Biomedical Research Program determine the sensorimotor and cognitive consequences of CNS reorganization resulting from exposure to microgravity. These are not currently being done. With regard to teleoperation and telepresence, virtual environments are being developed for use in training and as experimental tools. As these techniques reach the required level of sophistication, their usefulness in controlling equipment and robots remotely will be evaluated. Virtual displays are being developed as part of two projects funded through NASA’s Advanced Human Support Technologies program, one of which is based at ARC. Head-mounted see-through displays as well as three-dimensional spatial displays are being developed with the objective of using these to study human perception and mobility. Ultimately, these displays will be used as tools to train astronauts for extravehicular and intravehicular activity, both preflight and also in flight on the ISS using the Virtual Environment Generator. The Strategy report recommended that preliminary studies be conducted on the effects of microgravity on human sensory and motor cortical maps using fMRI and that strategies be developed to determine the sensorimotor and cognitive consequences of CNS reorganization resulting from exposure to microgravity. At present, these are not being done. Virtual environments and head-mounted displays are being developed, and these will be used in teleoperation and for training astronauts. SUMMARY NASA’s research program has made major advances in characterizing changes in posture and balance experienced by astronauts during spaceflight and in understanding the responses of the visual-vestibular system to altered gravitational conditions. However, as recommended in the Strategy report, studies are needed to determine the effects of microgravity on human sensory and motor cortical maps using fMRI, and how microgravity may affect CNS reorganization in general and sensorimotor and cognitive functions in particular. At present, animal studies are supported by NASA to characterize certain basic functions of the peripheral vestibular system in university-based laboratories. Little or no progress has been made on understanding how the central vestibular system is affected by microgravity. Further, there appears to be little, if any, linkage between animal-based and human-based research. In the future, it would be desirable to find a more effective mechanism for integrating information obtained from animal and human studies. BIBLIOGRAPHY Harm, D.L., L. Putcha, B.K. Sekula, and K.L. Berens. 1999. Effects of promethazine on performance during simulated shuttle landings. Pp. 148-149 in Proceedings of First Biennial Biomedical Investigators’ Workshop, January 11-13, 1999, League City, Texas. Houston, Tex.: NASA and Universities Space Research Association (USRA). National Aeronautics and Space Administration (NASA). 1997. Task Force Report on Countermeasures: Final Report. Washington, D.C.: NASA. NASA. 1998. Life Sciences Program Tasks and Bibliography for FY 1998. Washington, D.C.: NASA. NASA. 1999. Countermeasure Evaluation and Validation Project Plan. Houston, Tex.: Johnson Space Center. National Research Council (NRC), Space Studies Board. 1998. A Strategy for Research in Space Biology and Medicine in the New Century. Washington, D.C.: National Academy Press.
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