Locomotor Dysfunction after Long-Duration Space Flight and Development of Countermeasures to Facilitate Faster Recovery

Exposure to the microgravity conditions of space flight induces adaptive modification in sensorimotor function allowing astronauts to operate in this unique environment. This adaptive state, however, is inappropriate for a 1-g environment. Consequently astronauts must spend time readapting to Earth s gravity following their return to Earth. During this readaptation period, alterations in sensorimotor function cause various disturbances in astronaut gait during postflight walking. They often rely more on vision for postural and gait stability and many report the need for greater cognitive supervision of motor actions that previous to space flight were fully automated. Over the last several years our laboratory has investigated postflight astronaut locomotion with the aim of better understanding how adaptive changes in underlying sensorimotor mechanisms contribute to postflight gait dysfunction. Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibularly-mediated reflexive head movement during locomotion after space flight. Furthermore, during motor learning, adaptive transitions are composed of two main mechanisms: strategic and plastic. Strategic mechanisms represent immediate and transitory modifications in control to deal with changes in the prevailing environment that, if prolonged, induce plastic mechanisms designed to automate new behavioral responses. The goal of the present study was to examine the contributions of sensorimotor subsystems such as the vestibular and body load sensing (BLS) somatosensory influences on head movement control during locomotion after long-duration space flight. Further we present data on the two motor learning processes during readaptation of locomotor function after long-duration space flight

Sex differences in functional limitations and the role of socioeconomic factors: a multi-cohort analysis

Background: Women are more likely to have functional limitations than are men, partly because of greater socioeconomic disadvantage. However, how sex differences vary by severity of functional limitations remains unclear. We examined sex differences in functional limitations, with attention to socioeconomic factors and severity of limitations. Methods: Longitudinal data on limitations in basic activities of daily living (ADL) and instrumental activities of daily living (IADL) and mobility activities were drawn from 62 375 participants from 14 countries. For ADL, IADL, and mobility, participants were categorised based on number of limited activities (0, 1, 2, or ≥3). Sex differences in limitations in four birth cohorts (1895–1929, 1930–38, 1939–45, and 1946–60) were analysed before and after adjustment for socioeconomic factors (education and labour force status). Findings: The prevalence of IADL and ADL limitations was higher in women than in men. After adjustment for socioeconomic factors, this sex difference was attenuated. The sex difference in IADL limitations at age 75 years (in the 1895–1929 cohort) was 3·7% before adjustment for socioeconomic factors (95% CI 2·6–4·7) and 1·7% (1·1–2·2) after adjustment. For ADL, the sex difference in limitations at age 75 years (in the 1895–1929 cohort) was 3·2% (2·3–4·1) before adjustment for socioeconomic factors and 1·4% (0·9–1·8) after adjustment. Sex differences in mobility limitations (16·1%, 95% CI 14·4–17·7) remained after adjustment for socioeconomic factors (14·3%, 12·7–15·9). After age 85 years, women were more likely to have three or more IADL or mobility limitations and men were more likely to have one or two limitations. Interpretation: Socioeconomic factors largely explain sex differences in IADL and ADL limitations but not mobility. Sex differences in mobility limitations in midlife are important targets for future research and interventions. Funding: National Institute on Aging, UK National Institute for Health Research, European Commission, and US Social Security Administration

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

The current study characterizes brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either the vestibulo-spinal reflex (saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)), or the ocular muscle response (utricle-mediated ocular VEMP (oVEMP)). Some researchers have reported that air-conducted skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for the subjects. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying otolith-specific deficits, including gait and balance problems that astronauts experience upon returning to earth. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that skull taps elicit similar patterns of cortical activity as the auditory tone bursts, and previous vestibular imaging studies. Subjects wore bilateral MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in the supine position, with eyes closed. Subjects received both forms of the stimulation in a counterbalanced fashion. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular system, resulting in the vestibular cortical response. Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory tone burst elicited vestibular evoked myogenic potentials, indicated by eye muscle responses. We further assessed subjects' postural control and its correlation with vestibular cortical activity. Our results provide the first evidence of using skull taps to elicit vestibular activity inside the MRI scanner. By conducting conjunction analyses we showed that skull taps elicit the same activation pattern as auditory tone bursts (superior temporal gyrus), and both modes of stimulation activate previously identified vestibular cortical regions. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects. This further supports that the skull tap could replace auditory tone burst stimulation in clinical interventions and basic science research. Moreover, we observed that greater vestibular activation is associated with better balance control. We showed that not only the quality of balance (indicated by the amount of body sway) but also the ability to maintain balance for a longer time (indicated by the balance time) was associated with individuals' vestibular cortical excitability. Our findings support an association between vestibular cortical activity and individual differences in balance. In sum, we found that the skull tap stimulation results in activation of canonical vestibular cortex, suggesting an equally valid, but more tolerable stimulation method compared to auditory tone bursts. This is of high importance in longitudinal vestibular assessments, in which minimizing aversive effects may contribute to higher protocol adherence

Effects of Normal Aging on Visuo-Motor Plasticity

Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuomotor plasticity is a form of behavioral neural plasticity which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into a microgravity or underwater environment. In order to determine the effects of aging on visuomotor plasticity, we chose the simple and easily measured paradigm of visual-motor re-arrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel analyses for 73 subjects aged 20 to 80 years. We found no statistically significant difference in measures of visuomotor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity

Sex differences and the role of education in cognitive ageing: analysis of two UK-based prospective cohort studies

BACKGROUND: Previous studies have shown an excess risk of Alzheimer's disease and related dementias among women. Education is thought to have a causal association with dementia onset. We aimed to investigate the role of education in influencing sex differences in cognitive ageing. METHODS: We analysed data from two prospective cohort studies in the UK; the English Longitudinal Study of Ageing (ELSA) and the Whitehall II study, to assess sex differences in cognitive performance and cognitive decline by birth cohort (birth year 1930-38, 1939-45, or 1946-55), before and after adjustment for education, and by high and low education level. Memory was assessed using immediate recall, for which data were available from all waves of the ELSA (2002-14) and Whitehall II (1997-2015) studies. Fluency was assessed using a semantic fluency test based on an animal naming task, with data available from all waves of the Whitehall II study and waves one to five (2002-10) and wave seven (2014) of the ELSA study. Cognitive scores were standardised separately in each study based on the mean and SD of the corresponding test among participants aged 50-59 years with secondary education. FINDINGS: 15 924 participants were included from the two studies. In pooled analyses, women had better memory scores than men in all birth cohorts, irrespective of adjustment for education (eg, at age 60 years, birth cohort 1930-38, mean difference between sexes [male scores minus female scores] -0·25 SDs [95% CI -0·32 to -0·19] after adjustment for education), and in both education level groups. Memory decline was faster in men than in women (at age 60 years, birth cohort 1946-55, mean difference in 13-year change -0·15 SDs [-0·20 to -0·09]; after adjustment for education -0·14 SDs [-0·20 to -0·08]). Men had better fluency scores than women in earlier birth cohorts and in the low education group (at age 60 years, birth cohort 1930-38, mean difference 0·20 SDs [95% CI 0·05 to 0·36]); but women had better fluency scores than men in later birth cohorts and in the high education group (at age 60 years, birth cohort 1946-55, mean difference -0·17 SDs [-0·24 to -0·10]). No sex differences were observed for fluency decline. INTERPRETATION: Our findings suggest that decreasing disparities between sexes in education, due to secular increases in educational opportunities, could attenuate sex differences in dementia risk and cognitive decline in the future. FUNDING: National Institute on Aging, National Institutes of Health; UK Medical Research Council; British Heart Foundation; and National Institute for Health Research

Understanding the Effects of Spaceflight on Head-trunk Coordination during Walking and Obstacle Avoidance

Prolonged exposure to spaceflight conditions results in a battery of physiological changes, some of which contribute to sensorimotor and neurovestibular deficits. Upon return to Earth, functional performance changes are tested using the Functional Task Test (FTT), which includes an obstacle course to observe postflight balance and postural stability, specifically during turning. The goal of this study was to quantify changes in movement strategies during turning events by observing the latency between headandtrunk coordinated movements. It was hypothesized that subjects experiencing neurovestibular adaptations would exhibit headtotrunk locking ('en bloc' movement) during turning, exhibited by a decrease in latency between head and trunk movement. FTT data samples were collected from ISS missions. Samples were analyzed three times preexposure, immediately postexposure (1 day post) and 2to3 times during recovery from the microgravity environment. Two 3D inertial measurements units (XSens MTx) were attached to subjects, one on the head and one on the upper back. This study focused primarily on the yaw movements about the subject's center of rotation. Time differences (latency) between head and trunk movement were calculated at two points on the obstacle course: the first turn to enter the obstacle course (approximately 90 turn) and averaged across a slalom obstacle portion, consisting of three turns (approximately three 90 turns). Preliminary analysis of the data shows a trend toward decreasing headtotrunk movement latency during postflight ambulation in slalom turning after reintroduction to Earth gravity in ISS astronauts. It is clear that changes in movement strategies are adopted during exposure to the microgravity environment and upon reintroduction to a gravity environment. Most ISS subjects exhibit symptoms of neurovestibular changes ('en bloc head and trunk movement) which may impact their ability to perform postflight functional tasks

Developing Personalized Sensorimotor Adaptability Countermeasures for Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. In this paper we will be presenting results from our ground-based study that show how behavioral, brain imaging and genomic data may be used to predict individual differences in sensorimotor adaptability to novel sensorimotor environments. This approach will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure, functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes

Locomotor Dysfunction after Spaceflight: Characterization and Countermeasure Development

Astronauts returning from space flight show disturbances in locomotor control manifested by changes in various sub-systems including head-trunk coordination, dynamic visual acuity, lower limb muscle activation patterning and kinematics (Glasauer, et al., 1995; Bloomberg, et al., 1997; McDonald, et al., 1996; 1997; Layne, et al., 1997; 1998, 2001, 2004; Newman, et al., 1997; Bloomberg and Mulavara, 2003). These post flight changes in locomotor performance, due to neural adaptation to the microgravity conditions of space flight, affect the ability of crewmembers especially after a long duration mission to egress their vehicle and perform extravehicular activities soon after landing on Earth or following a landing on the surface of the Moon or Mars. At present, no operational training intervention is available pre- or in- flight to mitigate post flight locomotor disturbances. 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. 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 sensorimotor sub-systems to achieve safe and effective locomotion as soon as possible after space flight. We have previously confirmed that subjects participating in adaptive generalization training programs, using a variety of visuomotor distortions and different motor tasks from throwing to negotiating an obstacle course as the dependent measure, can learn to enhance their ability to adapt to a novel sensorimotor environment (Roller et al., 2001; Cohen et al. 2005). Importantly, this increased adaptability is retained even one month after completion of the training period. Our laboratory is currently developing adaptive generalization training procedures and the associated flight hardware to implement such a training program, using variations of visual flow, subject loading, and treadmill speed; during regular in-flight treadmill operations

Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance in a Discordant Sensory Environment

Astronauts exposed to microgravity face sensorimotor challenges incurred when readapting to a gravitational environment. Sensorimotor Adaptability (SA) training has been proposed as a countermeasure to improve locomotor performance during re-adaptation, and it is suggested that the benefits of SA training may be further enhanced by improving detection of weak sensory signals via mechanisms such as stochastic resonance when a non-zero level of stochastic white noise based electrical stimulation is applied to the vestibular system (stochastic vestibular stimulation, SVS). The purpose of this study was to test the efficacy of using SVS to improve short-term adaptation in a sensory discordant environment during performance of a locomotor task

Countermeasures to Enhance Sensorimotor Adaptability

During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The goal of our current project is to develop a sensorimotor adaptability (SA) training program to facilitate rapid adaptation to novel gravitational environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene that provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. We have conducted a series of studies that have shown: Training using a combination of modified visual flow and support surface motion during treadmill walking enhances locomotor adaptability to a novel sensorimotor environment. Trained individuals become more proficient at performing multiple competing tasks while walking during adaptation to novel discordant sensorimotor conditions. Trained subjects can retain their increased level of adaptability over a six months period. SA training is effective in producing increased adaptability in a more complex over-ground ambulatory task on an obstacle course. This confirms that for a complex task like walking, treadmill training contains enough of the critical features of overground walking to be an effective training modality. The structure of individual training sessions can be optimized to promote fast/strategic motor learning. Training sessions that each contain short-duration exposures to multiple perturbation stimuli allows subjects to acquire a greater ability to rapidly reorganize appropriate response strategies when encountering a novel sensory environment. Individual sensory biases (i.e. increased visual dependency) can predict adaptive responses to novel sensory environments suggesting that customized training prescriptions can be developed to enhance adaptability. These results indicate that SA training techniques can be added to existing treadmill exercise equipment and procedures to produce a single integrated countermeasure system to improve performance of astro/cosmonauts during prolonged exploratory space missions