Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight.

Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.

Prolonged Microgravity Affects Human Brain Structure and Function.

BACKGROUND AND PURPOSE: Widespread brain structural changes are seen following extended spaceflight missions. The purpose of this study was to investigate whether these structural changes are associated with alterations in motor or cognitive function. MATERIALS AND METHODS: Brain MR imaging scans of National Aeronautics and Space Administration astronauts were retrospectively analyzed to quantify pre- to postflight changes in brain structure. Local structural changes were assessed using the Jacobian determinant. Structural changes were compared with clinical findings and cognitive and motor function. RESULTS: Long-duration spaceflights aboard the International Space Station, but not short-duration Space Shuttle flights, resulted in a significant increase in total ventricular volume (10.7% versus 0%, P < .001, n = 12 versus n = 7). Total ventricular volume change was significantly associated with mission duration (r = 0.72, P = .001, n = 19) but negatively associated with age (r = -0.48, P = .048, n = 19). Long-duration spaceflights resulted in significant crowding of brain parenchyma at the vertex. Pre- to postflight structural changes of the left caudate correlated significantly with poor postural control; and the right primary motor area/midcingulate correlated significantly with a complex motor task completion time. Change in volume of 3 white matter regions significantly correlated with altered reaction times on a cognitive performance task (bilateral optic radiations, splenium of the corpus callosum). In a post hoc finding, astronauts who developed spaceflight-associated neuro-ocular syndrome demonstrated smaller changes in total ventricular volume than those who did not (12.8% versus 6.5%, n = 8 versus n = 4). CONCLUSIONS: While cautious interpretation is appropriate given the small sample size and number of comparisons, these findings suggest that brain structural changes are associated with changes in cognitive and motor test scores and with the development of spaceflight-associated neuro-optic syndrome.

Calibrating balance perturbation using electrical stimulation of the vestibular system.

BACKGROUND: Supra-threshold galvanic vestibular stimulation (GVS) can be used to challenge the balance control system by disrupting vestibular inputs. The goal of this study was to propose an objective method to assess variability across subjects in the minimum safe GVS level that causes maximum balance degradation. New method: Thirteen healthy young subjects stood on a compliant foam surface with their eyes closed and tried to maintain a stable upright stance. Variables related to the stability of the trunk and whole body were quantified to characterize the relationship between postural responses and GVS at amplitudes from 0 to 4.5 mA in 0.5 mA increments. The relationship between decrements in postural responses and GVS was linear up to a minimum GVS level (called KNEE). An increase in the stimulation level above that did not lead to any further degradation of balance performance. The KNEE was determined by iteratively performing linear fits to the performance measure at different stimulation levels. RESULTS: There were individual differences in KNEE; it was in the range of 1-2.5 mA across subjects. GVS caused an average performance decrement of 27-99% across six variables at the KNEE level compared to a no-stimulus condition. Comparison to existing methods: We propose a method to consistently attain the maximum level of impairment across subjects using the minimum current intensity, to minimize all types of adverse effects usually observed at high intensities. CONCLUSIONS: Individual differences in the disruption of posture control in response to GVS have important implications for testing and training paradigms.

Neural correlates of multi-day learning and savings in sensorimotor adaptation.

In the present study we evaluated changes in neural activation that occur over the time course of multiple days of sensorimotor adaptation, and identified individual neural predictors of adaptation and savings magnitude. We collected functional MRI data while participants performed a manual adaptation task during four separate test sessions over a three-month period. This allowed us to examine changes in activation and associations with adaptation and savings at subsequent sessions. Participants exhibited reliable savings of adaptation across the four sessions. Brain activity associated with early adaptation increased across the sessions in a variety of frontal, parietal, cingulate, and temporal cortical areas, as well as various subcortical areas. We found that savings was positively associated with activation in several striatal, parietal, and cingulate cortical areas including the putamen, precuneus, angular gyrus, dorsal anterior cingulate cortex (dACC), and cingulate motor area. These findings suggest that participants may learn how to better engage cognitive processes across days, potentially reflecting improvements in action selection. We propose that such improvements may rely on action-value assignments, which previously have been linked to the dACC and striatum. As correct movements are assigned a higher value than incorrect movements, the former are more likely to be performed again.

Multi-day Adaptation and Savings in Manual and Locomotor Tasks.

Using an individual differences approach, we evaluated whether manual and locomotor adaptation are associated in terms of adaptation and savings across days, and whether they rely on shared underlying mechanisms involving visuospatial working memory or visual field dependence. Participants performed a manual and a locomotor adaptation task during 4 separate test sessions over a 3-month period. Reliable adaptation and savings were observed for both tasks. It was further found that higher visuospatial working memory performance and lower visual field dependence scores were associated with faster learning in the manual and locomotor tasks, respectively. Moreover, adaptation rates were correlated between the 2 tasks in the final test session, suggesting that people may gradually be learning something generalizable about the adaptation process.

Prototype tests of vertical and torsional alignment nulling for screening vestibular function.

BACKGROUND: We have developed a non-invasive, behavioral measure of ocular alignment using a computer tablet, colored lenses, and touch screen software. OBJECTIVE: The goal of this study was to determine if these tests differentiate healthy controls from patients with vestibular disorders. METHODS: In the vertical alignment nulling test (VAN), subjects were asked to adjust a horizontal line that was offset vertically from a fixed horizontal line. In the torsional alignment nulling test (TAN) subjects were asked to adjust a line that was rotationally offset (i.e. clockwise) from a fixed horizontal line. We measured VAN and TAN in 14 healthy controls and 8 patients with known vestibular disorders. RESULTS: Patients had significantly worse scores than controls on TAN, (mean 2.2 vs 0.75, p = 0.01), and no differences for scores compared to controls on VAN, (mean 0.4 vs 0.8, p = 0.07). CONCLUSIONS: These results suggest that TAN, and possibly VAN, have potential for identifying misalignments in ocular position. After further technical development these tests might be useful in the future for screening patients in facilities that are not equipped to perform cervical and ocular vestibular evoked myogenic potentials.

Vestibular-somatosensory convergence in head movement control during locomotion after long-duration space flight.

Space flight causes astronauts to be exposed to adaptation in both the vestibular and body load-sensing somatosensory systems. The goal of these studies was to examine the contributions of vestibular and body load-sensing somatosensory influences on vestibular mediated head movement control during locomotion after long-duration space flight. Subjects walked on a motor driven treadmill while performing a gaze stabilization task. Data were collected from three independent subject groups that included bilateral labyrinthine deficient (LD) patients, normal subjects before and after 30 minutes of 40% bodyweight unloaded treadmill walking, and astronauts before and after long-duration space flight. Motion data from the head and trunk segments were used to calculate the amplitude of angular head pitch and trunk vertical translation movement while subjects performed a gaze stabilization task, to estimate the contributions of vestibular reflexive mechanisms in head pitch movements. Exposure to unloaded locomotion caused a significant increase in head pitch movements in normal subjects, whereas the head pitch movements of LD patients were significantly decreased. This is the first evidence of adaptation of vestibular mediated head movement responses to unloaded treadmill walking. Astronaut subjects showed a heterogeneous response of both increases and decreases in the amplitude of head pitch movement. We infer that body load-sensing somatosensory input centrally modulates vestibular input and can adaptively modify vestibularly mediated head-movement control during locomotion. Thus, space flight may cause central adaptation of the converging vestibular and body load-sensing somatosensory systems leading to alterations in head movement control.

Adaptive responses in eye-head-hand coordination following exposures to a virtual environment as a possible space flight analog.

Virtual reality environments (VRs) offer unique training opportunities, particularly for training astronauts and preadapting them to the novel sensory conditions of microgravity. The purpose of the current research was to compare disturbances in eye-head-hand (EHH) sensorimotor coordination produced by repeated exposures to VR systems. In general, we observed significant increases in position errors for both horizontal and vertical targets. The largest decrements were observed immediately following exposure to VR and showed general recovery within 6 hours across each test session, but not across days. Subjects generally showed faster reaction times across days. These findings provide some direction for developing training schedules for VR users that facilitate adaptation and support the idea that VRs may serve as an analog for sensorimotor effects of spaceflight.

Optic flow dominates visual scene polarity in causing adaptive modification of locomotor trajectory.

Locomotion and posture are influenced and controlled by vestibular, visual and somatosensory information. Optic flow and scene polarity are two characteristics of a visual scene that have been identified as being critical in how they affect perceived body orientation and self motion. The goal of this study was to determine the role of optic flow and visual scene polarity on adaptive modification in locomotor trajectory. An object is said to have visual polarity, or to be "visually polarized", when it contains an identifiable principal axis with one end distinct from the other. Two computer-generated virtual reality scenes were shown to subjects during 20 min of treadmill walking. One scene was a highly polarized scene, while the other was composed of objects displayed in a non-polarized fashion. Both virtual scenes depicted constant rate self motion equivalent to walking counterclockwise around the perimeter of a room. Subjects performed Stepping Tests blindfolded before and after scene exposure to assess adaptive changes in locomotor trajectory. Subjects showed a significant difference in heading direction, between pre- and post-adaptation Stepping Tests, when exposed to either scene during treadmill walking. However, there was no significant difference in the subjects' heading direction between the two visual scene polarity conditions. Therefore, it was inferred from these data that optic flow has a greater role than visual polarity in influencing adaptive locomotor function.

Exposure to a rotating virtual environment during treadmill locomotion causes adaptation in heading direction.

The objective of this study was to investigate the adaptive effects of variation in the direction of optic flow, experienced during linear treadmill walking, on modifying locomotor trajectory. Subjects (n=30) walked on a motorized linear treadmill at 4.0 km h(-1) for 24 min while viewing the interior of a 3D virtual scene projected on to a screen 1.5 m in front of them. The virtual scene depicted constant self-motion equivalent to either (1) walking around the perimeter of a room to one's left (Rotating Room group) or (2) walking down the center of a hallway (Infinite Corridor group). The scene was static for the first 4 min and then constant rate self-motion was simulated for the remaining 20 min. Before and after the treadmill locomotion adaptation period subjects performed five stepping trials. In each trial they marched in place to the beat of a metronome at 90 steps min(-1) for a total of 100 steps while blindfolded in a quiet room. The subject's final heading direction (deg) and final X (fore-aft, cm) and final Y (medio-lateral, cm) positions were measured for each trial. During the treadmill locomotion adaptation period subjects' 3D torso position was measured. We found that subjects in the Rotating Room group, as compared with the Infinite Hallway group: (1) showed significantly greater deviation during post-exposure testing in the heading direction and Y position opposite to the direction of optic flow experienced during treadmill walking; and (2) showed a significant monotonically increasing torso yaw angular rotation bias in the direction of optic flow during the treadmill adaptation exposure period. Subjects in both groups showed greater forward translation (in the +X direction) during the post-treadmill stepping task that differed significantly from their pre-exposure performance. Subjects in both groups reported no perceptual deviation in position during the stepping tasks. We infer that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of sensorimotor integration in the control of position and trajectory during locomotion, which functionally reflects adaptive changes in the integration of visual, vestibular, and proprioceptive cues. Such an adaptation in the control of position and heading direction during locomotion, because of the congruence of sensory information, demonstrates the potential for adaptive transfer between sensorimotor systems and suggests a common neural site for processing and self-motion perception and concurrent adaptation in motor output.

Full-body gaze control mechanisms elicited during locomotion: effects of VOR adaptation.

We have previously shown that multiple, interdependent, full- body sensorimotor subsystems aid gaze stabilization during locomotion. In the present study we investigated how the full-body gaze control system responds following exposure to visual-vestibular conflict known to adaptively modify vestibulo-ocular reflex (VOR) function. Subjects (n = 14) walked (6.4 km/h) on a motorized treadmill before and after they were exposed to 0.5X minifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. Results indicate that, following the exposure the major changes that subjects showed were to: 1) decrease the amplitude of head pitch and vertical translation of the torso movement with respect to space; 2) increase the amount of knee and ankle flexion during the initial stance phase of the gait cycle. A correlation analysis showed that: 1) changes in the head pitch significantly co-varied with that of the vertical torso translation 2) changes in the knee flexion significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle 3) changes in the vertical torso translation significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle. Thus we infer that the changes in the magnitude after VOR adaptation in comparison to their pre adaptation responses serve to aid gaze stabilization during locomotion. The significant covariation of the changes between subsystems provides further evidence that the full body contributes to gaze stabilization during locomotion, and its different functional elements are subject to adaptive reorganization following exposure to visual-vestibular conflict.

Variable practice with lenses improves visuo-motor plasticity.

Novel sensorimotor situations present a unique challenge to an individual's adaptive ability. Using the simple and easily measured paradigm of visual-motor rearrangement created by the use of visual displacement lenses, we sought to determine whether an individual's ability to adapt to visuo-motor discordance could be improved through training. Subjects threw small balls at a stationary target during a 3-week practice regimen involving repeated exposure to one set of lenses in block practice (x 2.0 magnifying lenses), multiple sets of lenses in variable practice (x 2.0 magnifying, x 0.5 minifying and up-down reversing lenses) or sham lenses. At the end of training, adaptation to a novel visuo-motor situation (20-degree right shift lenses) was tested. We found that (1) training with variable practice can increase adaptability to a novel visuo-motor situation, (2) increased adaptability is retained for at least 1 month and is transferable to further novel visuo-motor permutations and (3) variable practice improves performance of a simple motor task even in the undisturbed state. These results have implications for the design of clinical rehabilitation programs and countermeasures to enhance astronaut adaptability, facilitating adaptive transitions between gravitational environments.

Conditions for interference versus facilitation during sequential sensorimotor adaptation.

We investigated how sensorimotor adaptation acquired during one experimental session influenced the adaptation in a subsequent session. The subjects' task was to track a visual target using a joystick-controlled cursor, while the relationship between joystick and cursor position was manipulated to introduce a sensorimotor discordance. Each subject participated in two sessions, separated by a pause of 2 min to 1 month duration. We found that adaptation was achieved within minutes, and persisted in the memory for at least a month, with only a small decay (experiment A). When the discordances administered in the two sessions were in mutual conflict, we found evidence for task interference (experiment B). However, when the discordances were independent, we found facilitation rather than interference (experiment C); the latter finding could not be explained by the use of an "easier" discordance in the second session (experiment D). We conclude that interference is due to an incompatibility between task requirements, and not to a competition of tasks for short-term memory. We further conclude that the ability to adapt to a sensorimotor discordance can be improved by practicing with an unrelated discordance.

Patterns of transfer of adaptation among body segments.

Two experiments were conducted in order to determine the patterns of transfer of visuomotor adaptation between arm and head pointing. An altered gain of display of pointing movements was used to induce a conflict between visual and somatosensory representations. Two subject groups participated in Experiment 1: group 1 adapted shoulder pointing movements, and group 2 adapted wrist pointing movements to a 0.5 gain of display. Following the adaptation regimen, subjects performed a transfer test in which the shoulder group performed wrist movements and the wrist group performed shoulder movements. The results demonstrated that both groups displayed typical adaptation curves, initially undershooting the target followed by a return to baseline performance. Transfer tests revealed that both groups had high transfer of the acquired adaptation to the other joint. Experiment 2 followed a similar design except that group 1 adapted head pointing movements and group 2 adapted arm pointing movements. The arm adaptation had high transfer to head pointing while the head adaptation had very little transfer to arm pointing. These results imply that, while the arm segments may share a common target representation for goal-directed actions, individual but functionally dependent target representations may exist for the control of head and arm movements.

Effect of long-duration spaceflight on postural control during self-generated perturbations.

This report is the first systematic evaluation of the effects of prolonged weightlessness on the bipedal postural control processes during self-generated perturbations produced by voluntary upper limb movements. Spaceflight impacts humans in a variety of ways, one of which is compromised postflight postural control. We examined the neuromuscular activation characteristics and center of pressure (COP) motion associated with arm movement of eight subjects who experienced long-duration spaceflight (3--6 mo) aboard the Mir space station. Surface electromyography, arm acceleration, and COP motion were collected while astronauts performed rapid unilateral shoulder flexions before and after spaceflight. Subjects generally displayed compromised postural control after flight, as evidenced by modified COP peak-to-peak anterior-posterior and mediolateral excursion, and pathlength relative to preflight values. These changes were associated with disrupted neuromuscular activation characteristics, particularly after the completion of arm acceleration (i.e., when subjects were attempting to maintain upright posture in response to self-generated perturbations). These findings suggest that, although the subjects were able to assemble coordination modes that enabled them to generate rapid arm movements, the subtle control necessary to maintain bipedal equilibrium evident in their preflight performance is compromised after long-duration spaceflight.

Context-dependent arm pointing adaptation.

We sought to determine the effectiveness of head posture as a contextual cue to facilitate adaptive transitions in manual control during visuomotor distortions. Subjects performed arm pointing movements by drawing on a digitizing tablet, with targets and movement trajectories displayed in real time on a computer monitor. Adaptation was induced by presenting the trajectories in an altered gain format on the monitor. The subjects were shown visual displays of their movements that corresponded to either 0.5 or 1.5 scaling of the movements made. Subjects were assigned to three groups: the head orientation group tilted the head towards the right shoulder when drawing under a 0.5 gain of display and towards the left shoulder when drawing under a 1.5 gain of display; the target orientation group had the home and target positions rotated counterclockwise when drawing under the 0.5 gain and clockwise for the 1.5 gain; the arm posture group changed the elbow angle of the arm they were not drawing with from full flexion to full extension with 0.5 and 1.5 gain display changes. To determine if contextual cues were associated with display alternations, the gain changes were returned to the standard (1.0) display. Aftereffects were assessed to determine the efficacy of the head orientation contextual cue compared to the two control cues. The head orientation cue was effectively associated with the multiple gains. The target orientation cue also demonstrated some effectiveness while the arm posture cue did not. The results demonstrate that contextual cues can be used to switch between multiple adaptive states. These data provide support for the idea that static head orientation information is a crucial component to the arm adaptation process. These data further define the functional linkage between head posture and arm pointing movements.

Effects of adaptation of vestibulo-ocular reflex function on manual target localization.

The goal of the present study was to determine if adaptive modulation of vestibulo-ocular reflex (VOR) function is associated with commensurate alterations in manual target localization. To measure the effects of adapted VOR on manual responses we developed the Vestibular-Contingent Pointing Test (VCP). In the VCP test, subjects pointed to a remembered target following passive whole body rotation in the dark. In the first experiment, subjects performed VCP before and after wearing 0.5X minifying lenses that adaptively attenuate horizontal VOR gain. Results showed that adaptive reduction in horizontal VOR gain was accompanied by a commensurate change in VCP performance. In the second experiment, bilaterally labyrinthine deficient (LD) subjects were tested to confirm that vestibular cues were central to the spatial coding of both eye and hand movements during VCP. LD subjects performed significantly worse than normal subjects. These results demonstrate that adaptive change in VOR can lead to alterations in manual target localization.