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At least 55 records · Page 3

Neural processing of gravito-inertial cues in humans. I. Influence of the semicircular canals following post-rotatory tilt

Sensory systems often provide ambiguous information. Integration of various sensory cues is required for the CNS to resolve sensory ambiguity and elicit appropriate responses. The vestibular system includes two types of sensors: the semicircular canals, which measure head rotation, and the otolith organs, which measure gravito-inertial force (GIF), the sum of gravitational force and inertial force due to linear acceleration. According to Einstein's equivalence principle, gravitational force is indistinguishable from inertial force due to linear acceleration. As a consequence, otolith measurements must be supplemented with other sensory information for the CNS to distinguish tilt from translation. The GIF resolution hypothesis states that the CNS estimates gravity and linear acceleration, so that the difference between estimates of gravity and linear acceleration matches the measured GIF. Both otolith and semicircular canal cues influence this estimation of gravity and linear acceleration. The GIF resolution hypothesis predicts that inaccurate estimates of both gravity and linear acceleration can occur due to central interactions of sensory cues. The existence of specific patterns of vestibuloocular reflexes (VOR) related to these inaccurate estimates can be used to test the GIF resolution hypothesis. To investigate this hypothesis, we measured eye movements during two different protocols. In one experiment, eight subjects were rotated at a constant velocity about an earth-vertical axis and then tilted 90 degrees in darkness to one of eight different evenly spaced final orientations, a so-called "dumping" protocol. Three speeds (200, 100, and 50 degrees /s) and two directions, clockwise (CW) and counterclockwise (CCW), of rotation were tested. In another experiment, four subjects were rotated at a constant velocity (200 degrees /s, CW and CCW) about an earth-horizontal axis and stopped in two different final orientations (nose-up and nose-down), a so-called "barbecue" protocol. The GIF resolution hypothesis predicts that post-rotatory horizontal VOR eye movements for both protocols should include an "induced" VOR component, compensatory to an interaural estimate of linear acceleration, even though no true interaural linear acceleration is present. The GIF resolution hypothesis accurately predicted VOR and induced VOR dependence on rotation direction, rotation speed, and head orientation. Alternative hypotheses stating that frequency segregation may discriminate tilt from translation or that the post-rotatory VOR time constant is dependent on head orientation with respect to the GIF direction did not predict the observed VOR for either experimental protocol.

Non-NASA Center↗

Torsional vestibulo-ocular reflex measurements for identifying otolith asymmetries possibly related to space motion sickness susceptibility

Recent studies by Diamond and Markham have identified significant correlations between space motion sickness susceptibility and measures of disconjugate torsional eye movements recorded during parabolic flights. These results support an earlier proposal by von Baumgarten and Thumler which hypothesized that an asymmetry of otolith function between the two ears is the cause of space motion sickness. It may be possible to devise experiments that can be performed in the 1 g environment on earth that could identify and quantify the presence of asymmetric otolith function. This paper summarizes the known physiological and anatomical properties of the otolith organs and the properties of the torsional vestibulo-ocular reflex which are relevant to the design of a stimulus to identify otolith asymmetries. A specific stimulus which takes advantage of these properties is proposed.

Non-NASA Center↗

A reevaluation of the vestibulo-ocular reflex: new ideas of its purpose, properties, neural substrate, and disorders

Conventional views of the vestibulo-ocular reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved--locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (< 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome).

Review↗

Long Duration Head-Down Tilt Bed Rest Studies: Safety Considerations Regarding Vision Health

Visual symptoms reported in astronauts returning from long duration missions in low Earth orbit, including hyperopic shift, choroidal folds, globe flattening and papilledema, are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, safety considerations have been raised regarding the ocular health of head-down tilt (HDT) bed rest subjects. HDT is a widely used ground ]based analog that simulates physiological changes of spaceflight, including fluid shifts. Thus, vision monitoring has been performed in bed rest subjects in order to evaluate the safety of HDT with respect to vision health. Here we report ocular outcomes in 9 healthy subjects (age range: 27-48 years; Male/Female ratio: 8/1) completing bed rest Campaign 11, an integrated, multidisciplinary 70-day 6 degrees HDT bed rest study. Vision examinations were performed on a weekly basis, and consisted of office-based (2 pre- and 2 post-bed rest) and in-bed testing. The experimental design was a repeated measures design, with measurements for both eyes taken for each subject at each planned time point. Findings for the following tests were all reported as normal in each testing session for every subject: modified Amsler grid, red dot test, confrontational visual fields, color vision and fundus photography. Overall, no statistically significant differences were observed for any of the measures, except for both near and far visual acuity, which increased during the course of the study. This difference is not considered clinically relevant as may result from the effect of learning. Intraocular pressure results suggest a small increase at the beginning of the bed rest phase (p=0.059) and lesser increase at post-bed rest with respect to baseline (p=0.046). These preliminary results provide the basis for further analyses that will include correlations between intraocular pressure change pre- and post-bed rest, and optical coherence tomography measurements of the retina.

Cromwell, Ronita L.↗

Torsional vestibulo-ocular reflex measurements for identifying otolith asymmetries possibly related to space motion sickness susceptibility

Recent studies have identified significant correlations between space motion sickness susceptibility and measures of disconjugate torsional eye movements recorded during parabolic flights. These results support an earlier proposal which hypothesized that an asymmetry of otolith function between the two ears is the cause of space motion sickness. It may be possible to devise experiments that can be performed in the 1 g environment on earth that could identify and quantify the presence of asymmetric otolith function. This paper summarizes the known physiological and anatomical properties of the otolith organs and the properties of the torsional vestibulo-ocular reflex which are relevant to the design of a stimulus to identify otolith asymmetries. A specific stimulus which takes advantage of these properties is proposed.

Peterka, Robert J.↗

NASA's Spaceflight Visual Impairment and Intracranial Hypertension Research Plan: An accelerated Research Collaboration

To date six long duration astronauts have experienced in flight visual changes and post flight signs of optic disc edema, globe flattening, choroidal folds, hyperoptic shifts and or raised intracranial pressure. In some cases the changes were transient while in others they are persistent with varying degrees of visual impairment. Given that all astronauts exposed to microgravity experience a cephalad fluid shift, and that both symptomatic and asymptomatic patients have exhibited optic nerve sheath edema on MRI, there is a high probability that all astronauts develop in-flight idiopathic intracranial hypertension to some degree. Those who are susceptible, have an increased likelihood of developing treatment resistant papilledema resulting in visual impairment and possible long-term vision loss. Such an acquired disability would have a profound mission impact and would be detrimental to the long term health of the astronaut. The visual impairment and increased intracranial pressure phenomenon appears to have multiple contributing factors. Consequently, the working "physiological fault bush" with elevated intracranial pressure at its center, is divided into ocular effects, and CNS and other effects. Some of these variables have been documented and or measured through operational data gathering, while others are unknown, undocumented and or hypothetical. Both the complexity of the problem and the urgency to find a solution require that a unique, non-traditional research model be employed such as the Accelerated Research Collaboration(TM) (ARC) model that has been pioneered by the Myelin Repair Foundation. In the ARC model a single entity facilitates and manages all aspects of the basic, translational, and clinical research, providing expert oversight for both scientific and managerial efforts. The result is a comprehensive research plan executed by a multidisciplinary team and the elimination of stove-piped research. The ARC model emphasizes efficient and effective communication between management and investigators; and real-time sharing of scientific discoveries in an effort to solve complex problems.

Otto, Christian↗

B Complex 5-Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

A subset of astronauts on International Space Station missions have experienced optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause of SANS is unknown, it is likely that there are multiple contributing factors, including genetic and environmental factors. Our recent work has shown that crewmembers with SANS have higher concentrations of metabolic biomarkers of impairments in the one-carbon metabolic pathway compared to unaffected astronauts - before, during, and after f light (1). B-vitamin status and the presence of one-carbon pathway single nucleotide polymorphism (SNP) variants predicted the incidence of SANS pathologies, including optic disc edema (2). Specifically, the G allele of methionine synthase reductase (MTRR) A66G and the C allele of serine hydroxymethyltransferase-1 (SHMT1) C1420T were associated with increased incidence of SANS pathologies (2). In a recent 30-d bed rest head-down tilt study with 0.5% CO2 exposure, 5 of 11 subjects developed optic disc edema (4) and the same SHMT1 C1420T and MTRR A66G genetic variants were associated with a larger increase in total retina thickness, a quantitative measure of optic disc edema (5). We published a multi-hit hypothesis of how genetics represents an indispensable element of SANS, which is a multifactorial problem (6). In brief: endothelial dysfunction secondary to genetic, biochemical/nutritional, and physiological (e.g., cardiovascular/fluid shift) f actors could lead to optic disc edema and the other ocular changes that occur in SANS. We expanded this hypothesis to include the possibility that genetic effects on B-vitamin status can alter nitric oxide synthesis and oxidative stress in the endothelium. This in turn could alter the turnover of structural components of the sclera, making it more susceptible to pathologic changes when faced with stressors related to the unrelenting headward fluid shift that occurs in weightlessness and strict head-down tilt bed rest (5). If the relationships that we have observed in flight and ground-based research hold true for the SANS Countermeasure Study, these genetic factors could predict who will be more susceptible to the development of SANS, and more importantly could also provide countermeasure options. As has been shown extensively in the literature, vitamin supplementation can serve to overcome genetic hindrances to one-carbon biochemistry and vascular physiology. Thus, based on our findings, publications, and hypotheses, supported by extensive supporting literature, we had hoped to test in the SANS Countermeasure Study the efficacy of a bioactive B-vitamin complex as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during strict 6-degree head down tilt bed rest, and ultimately in space f light. While the supplement is no longer planned to be tested in the SANS Countermeasure Study because of laws regulating supplementation studies like this costing much more than initially planned, we will assess the contribution of one-carbon pathway genetics and B-vitamin status to SANS risk.

S R Zwart↗

Effects of weightlessness on the development of the vestibular apparatus and ocular nystagmus in the rat

The chronic 2g centrifuge was constructed for testing weightlessness effects on development of vestibular apparatus and ocular nystagmus in the rat. Both the stationary and rotating rail tests were performed. A physiological review is presented on vestibular apparatus, along with a system analysis. Time constants and input threshold level of the system are also considered.

Clark, D. L.↗

Mapping by VESGEN of Blood Vessels in the Retinas of Astronauts Pre- and Post-Flight to the ISS

Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.

VESGEN↗

The cerebellum: a neuronal learning machine?

Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

Non-NASA Center↗

VIIP 2017 Clinical Update

INTRODUCTION: NASA's Space Medicine community knowledge regarding the "Vision Impairment Intracranial Pressure", or VIIP.has been evolving over time.. Various measures of occupational health related to this condition had to be determined and then plans/processes put into place. The most robust of these processes were inititated in 2010. This presentation will provide a clinic update of the astronaut occupational health data related to VIIP. METHODS: NASA and its international partners require its astronauts to undergo routine health measures deemed important to monitoring VIIP. The concern is that the spaceflight environment aboard ISS could cause some astronauts to have physiologic changes detrimental to either ongoing mission operations or long-term health related to the ocular system and possibly the CNS. Specific medical tests include but are not limited to brain/orbit MRI (NASA unique protocol), OCT, fundoscopy and ocular ultrasound. Measures are taken prior to spaceflight, in-flight and post-flight. Measures to be reported include incidence of disc edema, globe flattening, choroidal folds, ONSD and change in refractive error. RESULTS: 73 ISS astronauts have been evaluated at least partially for VIIP related measures. Of these individuals, approximately 1 in 7 have experienced disc edema. The prevalence of the other findings is more complicated as the medical testing has changed over time. Overall, 26 separate individuals have experienced at least one of the findings NASA has associated with VIIP Another confounding factor is most of the astronauts have prior spaceflight experience at the time of the "pre-flight" testing. DISCUSSION: In 2010 NASA and its US operating segment (USOS) partners (CSA, ESA and JAXA) began routine occupational monitoring and data collection for most VIIP related changes. Interpretation of that data is extremely challenging for several reasons. For example, the determination of disc edema is the most complete finding as we have had highly qualified optometrists routinely and competently performing post-flight funduscopic exams for the entirety of the ISS program. Yet in 2013 NASA added OCT to our in-flight suite of eye exams. Shortly after routine screening with the OCT, a new term appeared within VIIP vernacular - "subclinical disc edema". OCT has much greater ability to measure change within the retina and provides significantly more data to analyze, understand and communicate out. Communicating VIIP data clearly adds even more challenge. Historically we've reported data per eye and not necessarily per person. This has led to difficulty in understanding how many individuals have experienced "VIIP" within the aerospace medicine community. The presenter will attempt to provide clear and concise communication of VIIP findings.

Tarver, William↗

VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine

Currently, astronauts face significant health risks in future long-duration exploration missions such as colonizing the Moon and traveling to Mars. Numerous risks include greatly increased radiation exposures beyond the low earth orbit (LEO) of the ISS, and visual and ocular impairments in response to microgravity environments. The cardiovascular system is a key mediator in human physiological responses to radiation and microgravity. Moreover, blood vessels are necessarily involved in the progression and treatment of vascular-dependent terrestrial diseases such as cancer, coronary vessel disease, wound-healing, reproductive disorders, and diabetes. NASA developed an innovative, globally requested beta-level software, VESsel GENeration Analysis (VESGEN) to map and quantify vascular remodeling for application to astronaut and terrestrial health challenges. VESGEN mappings of branching vascular trees and networks are based on a weighted multi-parametric analysis derived from vascular physiological branching rules. Complex vascular branching patterns are determined by biological signaling mechanisms together with the fluid mechanics of multi-phase laminar blood flow.

astronaut↗

Minipigs as a Model to Study Separate and Combined Effects of Space Radiation and Altered Gravity on Cardiovascular disease, Spaceflight-Associated Neuro-Ocular Syndrome (SANS), and Central Nervous System (CNS) effects

Minipigs are a well-characterized animal model used to study thecardiovascular system, metabolism, bone, gastrointestinal tract,pancreas, liver, kidney, lung, immune system, central nervous system(white matter) etc. Due to their anatomical, physiological, andbiochemical similarities to humans, minipigs are considered atranslational model in biomedical research and development. Also, their large size and cognitive abilities allow collection of supplementary information regarding the central nervous system(BMed) and Spaceflight-Associated Neuro-Ocular Syndrome (SANS) risk.

Janapriya Saha↗

Thoracic Pressure Does Not Impact CSF Pressure via Compartment Compliance

Space acquired neuro-ocular syndrome (SANS) remains a difficult risk to characterize due to the complex multi-factorial etiology related to physiological responses to the spaceflight environment. Fluid shift and the resultant change on the Cardiovascular (CV) and cerebral spinal fluid systems (CSF) in the absence of gravity continue to be considered a contributing factor to the progression of SANS. In this study, we utilize a computational model of the CSF and CV interface to establish the sensitivity that intracranial pressure, and subsequently the optic nerve sheath pressure, exhibits due to variations in thoracic pressure, assuming the cranial perfusion pressure, i.e. mean arterial pressure (MAP) to central venous pressure (CVP), is known. Methods: The GRC Cross cutting computational modeling project created as model of the CSF and CV interaction within the cranial vault by extending the work of Stevens et al. [1] by modifying the representative anatomy to include a separate venous sinus, jugular veins, secondary veins and extra jugular pathways [2-3] to more adequately represent the vascular drainage pathways from the cranial vault (Figure 1). Assuming the MAP, CVP and thoracic pressure are known, we initiated this enhanced computational model assuming a supine positon and utilized a linear ramp to vary the thoracic pressure from the assumed supine state to the target pressure corresponding to set MAP and CVP values. The model generates the time based CSF pressure values (Figure2). Results and Conclusions: Following this analysis, CSF pressure shows significant independence from thoracic pressure changes (16 mmHg in thoracic pressure produces < 1mmHg change in CSF pressure), being mostly dependent on perfusion pressure. Similarly fluid redistribution is not predicted to be impacted over a level of 1mL. We note that this simulation represents an acute changes (order of 10's of minutes) and does not represent the long term effects.

Munster, Drayton W.↗

Dynamic properties of the human vestibulo-ocular reflex during head rotations in roll

We investigated the dynamic properties of the human vestibulo-ocular reflex (VOR) during roll head rotations in three human subjects using the magnetic search coil technique. In the first of two experiments, we quantify the behavior of the ocular motor plant in the torsional plane. The subject's eye was mechanically displaced into intorsion, extorsion or abduction, and the dynamic course of return of the eye to its resting position was measured. The mean predominant time constants of return were 210 msec from intorsion, 83 msec from extorsion, and 217 msec from abduction, although there was considerable variability of results from different trials and subjects. In the second experiment, we quantify the efficacy of velocity-to-position integration of the vestibular signal. Position-step stimuli were used to test the torsional or horizontal VOR, being applied with subjects heads erect or supine. After a torsional position-step, the eye drifted back to its resting position, but after a horizontal position-step the eye held its new horizontal position. To interpret these responses we used a simple model of the VOR with parameters of the ocular motor plant set to values determined during Exp 1. The time constant of the velocity-to-position neural integrator was smaller (typically 2 sec) in the torsional plane than in the horizontal plane (> 20 sec). No disconjugacy of torsional eye movements was observed. Thus, the dynamic properties of the VOR in roll differ significantly from those of the VOR in yaw, reflecting different visual demands placed on this reflex in these two planes.

NASA Discipline Neuroscience↗

The dynamic contributions of the otolith organs to human ocular torsion

We measured human ocular torsion (OT) monocularly (using video) and binocularly (using search coils) while sinusoidally accelerating (0.7 g) five human subjects along an earth-horizontal axis at five frequencies (0.35, 0.4, 0.5, 0.75, and 1.0 Hz). The compensatory nature of OT was investigated by changing the relative orientation of the dynamic (linear acceleration) and static (gravitational) cues. Four subject orientations were investigated: (1) Y-upright-acceleration along the interaural (y) axis while upright; (2) Y-supine-acceleration along the y-axis while supine; (3) Z-RED-acceleration along the dorsoventral (z) axis with right ear down; (4) Z-supine-acceleration along the z-axis while supine. Linear acceleration in the Y-upright, Y-supine and Z-RED orientations elicited conjugate OT. The smaller response in the Z-supine orientation appeared disconjugate. The amplitude of the response decreased and the phase lag increased with increasing frequency for each orientation. This frequency dependence does not match the frequency response of the regular or irregular afferent otolith neurons; therefore the response dynamics cannot be explained by simple peripheral mechanisms. The Y-upright responses were larger than the Y-supine responses (P < 0.05). This difference indicates that OT must be more complicated than a simple low-pass filtered response to interaural shear force, since the dynamic shear force along the interaural axis was identical in these two orientations. The Y-supine responses were, in turn, larger than the Z-RED responses (P < 0.01). Interestingly, the vector sum of the Y-supine responses plus Z-RED responses was not significantly different (P = 0.99) from the Y-upright responses. This suggests that, in this frequency range, the conjugate OT response during Y-upright stimulation might be composed of two components: (1) a response to shear force along the y-axis (as in Y-supine stimulation), and (2) a response to roll tilt of gravitoinertial force (as in Z-RED stimulation).

NASA Discipline Neuroscience↗