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Warren, L. E.

Publications and source records attributed to Warren, L. E..

Implementation of the NASA AG-Bed Rest Pilot

To examine the efficacy of artificial gravity (AG) as a countermeasure to spaceflight deconditioning, intermittent AG produced by a horizontal short-radius centrifuge (SRC) was utilized on human test subjects deconditioned by bed rest. This poster will present the subject screening, study design, logistics, and implementation of the 41 day pilot study conducted at the University of Texas Medical Branch, Galveston, TX bed rest facility. An extensive screening process was employed to exclude subjects that were dissimilar to the U.S. astronaut population. Candidates underwent a modified U.S. Air Force Class III physical and tests of bone density, cardiovascular fitness, vestibular system function, psychological fitness and centrifuge tolerance. 15 subjects completed the study; 7 control and 8 AG treatment. All provided written consent to volunteer after the nature of the study and its hazards were clearly explained to them. Standard conditions were strictly regulated; Ta = 72 +/- 2 F, humidity = 70 +/- 5%, light/dark cycle 16h:8h. All fluid intake (minimum 28.5 ml/kg body weight/day) and urine output was monitored. Caloric intake was adjusted as necessary to maintain body weight. Carbohydrate, fat and protein were provided in a ratio of 55:30:15. Phosphorus intake was 1400 mg/d, sodium intake was 2 mmol/kg/d, potassium intake was 1.3 mmol/kg/d, and dietary calcium intake was 1000 mg/d. A physician examined each subject daily. During the first 11 days of the study protocol, subjects were ambulatory, but confined to the facility. Subjects participated in multiple baseline tests of bone, muscle, cardiovascular, sensory-motor, immunological, and psychological function. On the 12th day, subjects entered the bed rest phase of the study, during which they were confined to strict 6? head down tilt bed rest for 21 days. Beginning 24 hrs into this period, treatment subjects received 1 hour daily exposures to artificial gravity which was produced by spinning the subjects on a 3.0 m radius SRC. They were oriented radially in the supine position so that the centrifugal force was aligned with their long body axis, and while spinning, they #stood# on a force plate, supporting the centrifugal loading (2.5 g at the feet, 1.0 g at the heart). The subject station allowed free translation over approximately 10 cm to ensure full loading of the lower extremities and to allow for anti-orthostatic muscle contractions. Control subjects were positioned on the centrifuge but did not spin. Following the bed rest phase, subjects were allowed to ambulate again, but remained within the facility for an additional 9 days and participated in multiple follow-up tests of physiological function.

Warren, L. E.

Development of Training Programs to Optimize Planetary Ambulation

Astronauts experience disturbances in functional mobility following their return to Earth due to adaptive responses that occur during exposure to the microgravity conditions of space flight. Despite significant time spent performing in-flight exercise routines, these training programs have not been able to mitigate postflight alterations in postural and locomotor function. Therefore, the goal of our two inter-related projects (NSBRI-ground based and ISS flight study, "Mobility") is to develop and test gait training programs that will serve to optimize functional mobility during the adaptation period immediately following space flight, thereby improving the safety and efficiency of planetary ambulation. The gait training program entails manipulating the sensory conditions of treadmill exercise to systematically challenge the balance and gait control system. This enhances the overall adaptability of locomotor function enabling rapid reorganization of gait control to respond to ambulation in different gravitational environments. To develop the training program, we are conducting a series of ground-based studies evaluating the training efficacy associated with variation in visual flow, body loading, and support surface stability during treadmill walking. We will also determine the optimal method to present training stimuli within and across training sessions to maximize both the efficacy and efficiency of the training procedure. Results indicate that variations in both visual flow and body unloading during treadmill walking leads to modification in locomotor control and can be used as effective training modalities. Additionally, the composition and timing of sensory challenges experienced during each training session has significant impact on the ability to rapidly reorganize locomotor function when exposed to a novel sensory environment. We have developed the capability of producing support surface variation during gait training by mounting a treadmill on a six-degree-of-freedom motion device. This hardware development will allow us to evaluate the efficacy of this type of training in conjunction with variation in visual flow and body unloading.

Bloomberg, J. J.

Development of a Countermeasure to Mitigate Postflight Locomotor Dysfunction

Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Evidence for the potential efficacy of an adaptive generalization gait training program can be obtained from numerous studies in the motor learning literature which have demonstrated that systematically varying the conditions of training enhances the ability of the performer to learn and retain a novel motor task. These variable practice training approaches have been used in applied contexts to improve motor skills required in a number of different sports. The central nervous system (CNS) can produce voluntary movement in an almost infinite number of ways. For example, locomotion can be achieved with many different combinations of joint angles, muscle activation patterns and forces. The CNS can exploit these degrees of freedom to enhance motor response adaptability during periods of adaptive flux like that encountered during a change in gravitational environment. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to normal. Rather the training regimen should facilitate the reorganization of available sensory and motor subsystems to achieve safe and effective locomotion as soon as possible after long duration space flight. Indeed, this approach has been proposed as a basic feature underlying effective neurological rehabilitation. We have previously confirmed that subjects participating in an adaptive generalization training program using a variety of visuomotor distortions and throwing as the dependent measure can learn to enhance their ability to adapt to a novel sensorimotor environment (Roller et al., 2001). Importantly, this increased adaptability was retained even one month after completion of the training period. Adaptive generalization has been observed in a variety of other tasks requiring sensorimotor transformations including manual control tasks and reaching (Bock et al., 2001, Seidler, 2003) and obstacle avoidance during walking (Lam and Dietz, 2004). Taken together, the evidence suggests that a training regimen exposing crewmembers to variation in locomotor conditions, with repeated transitions among states, may enhance their ability to learn how to reassemble appropriate locomotor patterns upon return from microgravity. We believe exposure to this type of training will extend crewmembers locomotor behavioral repertoires, facilitating the return of functional mobility after long duration space flight. In other words, our proposed training protocol will compel subjects to develop new behavioral solutions under varying sensorimotor demands. Over time subjects will learn to create appropriate locomotor solution more rapidly enabling acquisition of mobility sooner after long-duration space flight. A gait adaptability training program can be superimposed on nominal treadmill exercise activities thus ensuring that no additional crew time is required to perform this type of training regimen and that it can be implemented with current in-flight exercise systems available on the International Space Station.

Bloomberg, J. J.

The Use of Dynamic Visual Acuity as a Functional Test of Gaze Stabilization Following Space Flight

After prolonged exposure to a given gravitational environment the transition to another is accompanied by adaptations in the sensorimotor subsystems, including the vestibular system. Variation in the adaptation time course of these subsystems, and the functional redundancies that exist between them make it difficult to accurately assess the functional capacity and physical limitations of astro/cosmonauts using tests on individual subsystems. While isolated tests of subsystem performance may be the only means to address where interventions are required, direct measures of performance may be more suitable for assessing the operational consequences of incomplete adaptation to changes in the gravitational environment. A test of dynamic visual acuity (DVA) is currently being used in the JSC Neurosciences Laboratory as part of a series of measures to assess the efficacy of a countermeasure to mitigate postflight locomotor dysfunction. In the current protocol, subjects visual acuity is determined using Landolt ring optotypes presented sequentially on a computer display. Visual acuity assessments are made both while standing and while walking at 1.8 m/s on a motorized treadmill. The use of a psychophysical threshold detection algorithm reduces the required number of optotype presentations and the results can be presented immediately after the test. The difference between the walking and standing acuity measures provides a metric of the change in the subject s ability to maintain gaze fixation on the visual target while walking. This functional consequence is observable regardless of the underlying subsystem most responsible for the change. Data from 15 cosmo/astronauts have been collected following long-duration (approx. 6 months) stays in space using a visual target viewing distance of 4.0 meters. An investigation of the group mean shows a change in DVA soon after the flight that asymptotes back to baseline approximately one week following their return to earth. The performance of some subjects nicely parallels the stereotypical recovery curve observed in the group mean data. Others show dramatic changes in DVA from one test day to another. These changes may be indicative of a re-adaptation process that is not characterized by a steady improvement with the passage of time, but is instead a dynamic search for appropriate coordinative strategy to achieve the desired gaze stabilization goal. Ground-based data have been collected in our lab using DVA with one of the goals being to improve the DVA test itself. In one of these studies, the DVA test was repeated using a visual target viewing distance of 0.5 meters. While walking, the relative contributions of the otoliths and semi-circular canals that are required to stabilize gaze are affected by visual target viewing distance. It may be possible to exploit this using the current treadmill DVA test to differentially assess changes in these vestibular subsystems. The postflight DVA evaluations currently used have been augmented to include the near target version of the test. Preliminary results from these assessments, as well as the results from the ground-based tests will also be reported. DVA provides a direct measure of a subject's ability to see clearly in the presence of self-motion. The use of the current tests for providing a functionally relevant metric is evident. However, it is possible to expand the scope of DVA testing to include scenarios other than walking. A facility for measuring DVA in the presence of passive movements is being created. Using a mechanized platform to provide the perturbation, it should be possible to simulate aircraft and automobile vibration profiles. Used in conjunction with the far and near visual displays this facility should be able to assess a subject s ability to clearly see distant objects as well as those that appear on the dashboard or instrument control panel during functionally relevant situations.

Peters, B. T.

Development of Testing Methodologies to Evaluate Postflight Locomotor Performance

Crewmembers experience locomotor and postural instabilities during ambulation on Earth following their return from space flight. Gait training programs designed to facilitate recovery of locomotor function following a transition to a gravitational environment need to be accompanied by relevant assessment methodologies to evaluate their efficacy. The goal of this paper is to demonstrate the operational validity of two tests of locomotor function that were used to evaluate performance after long duration space flight missions on the International Space Station (ISS).

Mulavara, A. P.

Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

Space flight induces adaptive modification in sensorimotor function, allowing crewmembers to operate in the unique microgravity environment. This adaptive state, however, is inappropriate for a terrestrial environment. During a re-adaptation period upon their return to Earth, crewmembers experience alterations in sensorimotor function, causing various disturbances in perception, spatial orientation, posture, gait, and eye-head coordination. Following long duration space flight, sensorimotor dysfunction would prevent or extend the time required to make an emergency egress from the vehicle; compromising crew safety and mission objectives. We are investigating two types of motor learning that may interact with each other and influence a crewmember's ability to re-adapt to Earth's gravity environment. In strategic learning, crewmembers make rapid modifications in their motor control strategy emphasizing error reduction. This type of learning may be critical during the first minutes and hours after landing. In adaptive learning, long-term plastic transformations occur, involving morphological changes and synaptic modification. In recent literature these two behavioral components have been associated with separate brain structures that control the execution of motor strategies: the strategic component was linked to the posterior parietal cortex and the adaptive component was linked to the cerebellum (Pisella, et al. 2004). The goal of this paper was to demonstrate the relative contributions of the strategic and adaptive components to the re-adaptation process in locomotor control after long duration space flight missions on the International Space Station (ISS). The Functional Mobility Test (FMT) was developed to assess crewmember s ability to ambulate postflight from an operational and functional perspective. Sixteen crewmembers were tested preflight (3 sessions) and postflight (days 1, 2, 4, 7, 25) following a long duration space flight (approx 6 months) on the ISS. We have further analyzed the FMT data to characterize strategic and adaptive components during the postflight readaptation period. Crewmembers walked at a preferred pace through an obstacle course set up on a base of 10 cm thick medium density foam (Sunmate Foam, Dynamic Systems, Inc., Leicester, NC). The 6.0m X 4.0m course consisted of several pylons made of foam; a Styrofoam barrier 46.0cm high that crewmembers stepped over; and a portal constructed of two Styrofoam blocks, each 31cm high, with a horizontal bar covered by foam and suspended from the ceiling which was adjusted to the height of the crewmember s shoulder. The portal required crewmembers to bend at the waist and step over a barrier simultaneously. All obstacles were lightweight, soft and easily knocked over. Crewmembers were instructed to walk through the course as quickly and as safely as possible without touching any of the objects on the course. This task was performed three times in the clockwise direction and three times in the counterclockwise direction that was randomly chosen. The dependent measures for each trial were: time to complete the course (seconds) and the number of obstacles touched or knocked down. For each crewmember, the time to complete each FMT trial from postflight days 1, 2, 4, 7 and 25 were further analyzed. A single logarithmic curve using a least squares calculation was fit through these data to produce a single comprehensive curve (macro). This macro curve composed of data spanning 25 days, illustrates the re-adaptive learning function over the longer time scale term. Additionally, logarithmic curves were fit to the 6 data trials within each individual post flight test day to produce 5 separate daily curves. These micro curves, produced from data obtained over the course of minutes, illustrates the strategic learning function exhibited over a relative shorter time scale. The macro curve for all subjects exhibited adaptive motor learning patterns over the 25 day period. Howev, 9/16 crewmembers exhibited significant strategic motor learning patterns in their micro curves, as defined by m > 1 in the equation of the line y=m*LN(x) +b. These data indicate that postflight recovery in locomotor function involves both strategic and adaptive mechanisms. Future countermeasures will be designed to enhance both recovery processes.

Warren, L. E.

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Preliminary Results

Artificial gravity paradigms may offer effective, efficient, multi-system protection from the untoward effects of adaptation to the microgravity of space or the hypogravity of planetary surfaces. Intermittent artificial gravity (AG) produced by a horizontal short-radius centrifuge (SRC) has recently been utilized on human test subjects deconditioned by bed rest. This presentation will review preliminary results of a 41 day study conducted at the University of Texas Medical Branch, Galveston, TX bed rest facility. During the first eleven days of the protocol, subjects were ambulatory, but confined to the facility. They began a carefully controlled diet, and participated in multiple baseline tests of bone, muscle, cardiovascular, sensory-motor, immunological, and psychological function. On the twelfth day, subjects entered the bed rest phase of the study, during which they were confined to strict 6deg head down tilt bed rest for 21 days. Beginning 24 hrs into this period, treatment subjects received one hour daily exposures to artificial gravity which was produced by spinning the subjects on a 3.0 m radius SRC. They were oriented radially in the supine position so that the centrifugal force was aligned with their long body axis, and while spinning, they "stood" on a force plate, supporting the centrifugal loading (2.5 g at the feet, 1.0 g at the heart). The subject station allowed free translation over approximately 10 cm to ensure full loading of the lower extremities and to allow for anti-orthostatic muscle contractions. Control subjects were positioned on the centrifuge but did not spin. Following the bed rest phase, subjects were allowed to ambulate again, but remained within the facility for an additional 9 days and participated in multiple follow-up tests of physiological function.

Warren, L. E.

A Hypothetical Perspective on the Relative Contributions of Strategic and Adaptive Control Mechanisms in Plastic Recalibration of Locomotor Heading Direction

We have previously shown that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of the control of position and trajectory during over-ground locomotion, which functionally reflects adaptive changes in the sensorimotor integration of visual, vestibular, and proprioceptive cues (Mulavara et al., 2005). The objective of this study was to investigate how strategic changes in torso control during exposure to simulated rotary self-motion during treadmill walking influences adaptive modification of locomotor heading direction during over-ground stepping.

Richards, J. T.

Development of an Inflight Countermeasure to Mitigate Postflight Gait Dysfunction

Following spaceflight crewmembers experience gait and postural instabilities due to inflight adaptive alterations in sensorimotor function. These changes can pose a risk to crew safety if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. At present, no operational countermeasure is available to mitigate postflight locomotor disturbances. Therefore, the goal of this study is to develop an inflight training regimen that facilitates the recovery of locomotor function after long-duration spaceflight. The countermeasure we are developing is based on the concept of variable practice. During this type of training the subject gains experience producing the appropriate adaptive motor behavior under a variety of sensory conditions and response constraints. This countermeasure is built around current ISS treadmill exercise activities. Crewmembers will conduct their nominal inflight treadmill exercise while being exposed to variations in visual flow patterns. These variations will challenge the postural and locomotor systems repeatedly, thereby promoting adaptive reorganization in locomotor behavior. As a result of this training a subject learns to solve a class of motor problems, rather than a specific motor solution to one problem, Le., the subject learns response generalizability or the ability to "learn to learn" under a variety of environmental constraints. We anticipate that this training will accelerate recovery of postural and locomotor function during readaptation to gravitational environments following spaceflight facilitating neural adaptation to unit (Earth) and partial (Mars) gravity after long-duration spaceflight. The study calls for one group of subjects to perform the inflight treadmill training regimen while a control group of subjects performs only the nominal exercise procedures. Locomotor function in both groups is assessed before and after spaceflight using two tests of gait function: The Integrated Treadmill Locomotion Test (ITLT) and the Functional Mobility Test (FMT). The ITLT characterizes alterations in the integrated function of multiple sensorimotor subsystems responsible for the control of locomotion. This test calls for subjects to walk on a motorized treadmill while we assess changes in dynamic postural stability, head-trunk coordination, short-latency head stabilization responses, dynamic visual acuity, lower limb coordination strategies and gait cycle timing. To make these assessments we measure the following parameters while subjects walk on the treadmill: 1) full body 3-dimensional kinematics using a motion capture system (Motion Analysis Corp., Santa Rosa, CA); 2) the shock-wave transmitted from heel-strike to the head using triaxial accelerometers placed on the tibia and head (Entran, Fairfield, NJ); 3) vertical forces using an instumented treadmill (Kistler Instrument Corp., Amherst, NY); 4) Dynamic visual acuity using Landolt Cs presented on a laptop computer located 4m from the eyes and 5) Gait cycle timing using foot-switches (Motion Lab Systems, Inc., Baton Rouge, LA) attached to the plantar surface of each shoe at the heel and toe. The FMT evaluates s. subject's ability to perform challenging locomotor maneuvers similar to those encountered during an egress from a space vehicle. Subjects step over and duck under obstacles along with negotiating a series of pylons set up on a base of 10 cm thick medium density foam. The dependent measures for the FMT are time to complete the course and the number of obstacles touched. To date, we have collected pre and postflight locomotion data from Expeditions 5-9 who will serve as part of the control group for this study. Preliminary results comparing the recovery rates in gait control sub-systems obtained from the ITLT and FMT performance showed two recovery patterns: 1) a concordant recovery trend between gait control parameters and FMT performance indicating a restitution pattern of recovery and 2) gait controecovery that lagged recovery in FMT performance suggesting that improvement in locomotor function was attained through a pattern of substitution. These data suggest that recovery of postflight locomotor function may occur through adaptive mechanisms that lead to either restitution or substitution of function. Understanding the modes of postflight readaptation has implications for countermeasure development and testing and in astronaut postflight rehabilitation.

Bloomberg, J. J.

Effects of 2 G on adiposity, leptin, lipoprotein lipase, and uncoupling protein-1 in lean and obese Zucker rats

Male Zucker rats were exposed to 2 G for 8 wk to test the hypothesis that the leptin regulatory pathway contributes to recovery from effects of 2 G on feeding, growth, and nutrient partitioning. After initial hypophagia, body mass-independent food intake of the lean rats exposed to 2 G surpassed that of the lean rats maintained at 1 G, but food intake of the obese rats exposed to 2 G remained low. After 8 wk at 2 G, body mass and carcass fat were less in both genotypes. Leptin and percent fat were lower in lean rats exposed to 2 G vs. 1 G but did not differ in obese rats exposed to 2 G vs. 1 G. Although exposure to 2 G did not alter uncoupling protein-1 levels, it did elicit white fat pad-specific changes in lipoprotein lipase activity in obese but not lean rats. We conclude that 2 G affects both genotypes but that the lean Zucker rats recover their food intake and growth rate and retain "normal" lipoprotein lipase activity to a greater degree than do the obese rats, emphasizing the importance of a functional leptin regulatory pathway in this acclimation.

NASA Discipline Regulatory Physiology

Gravity and body mass regulation

The effects of altered gravity on body mass, food intake, energy expenditure, and body composition are examined. Metabolic adjustments are reviewed in maintenance of energy balance, neural regulation, and humoral regulation are discussed. Experiments with rats indicate that genetically obese rats respond differently to hypergravity than lean rats.

NASA Discipline Regulatory Physiology