Stochastic resonance (SR) is a mechanism whereby noise can assist and hence enhance the response of neural systems by detecting sub-threshold signals. SR thus enables the enhanced detection of relevant sensory signals. SR stimulation using imperceptible noisy vibratory or electrical stimulation has been shown to improve balance function in normal young and elderly subjects, stroke patients, and in the rehabilitation of functional ankle joint instabilities. This project specifically has used imperceptible levels of electrical stimulation of the vestibular system (VSR) as the proposed countermeasure to improve performance in egress tasks. The project has also conducted a series of studies to document human visual performance during simulated low frequency dynamic perturbations and further investigate the efficacy of VSR stimulation on physiological and perceptual responses during otolith-canal conflicts and dynamic perturbations.

Goal 1: The objective of two separate studies that were conducted was to document human visual performance during simulated wave motion in the 0.1 to 2.0 Hz range. The main findings of both studies showed that dynamic visual acuity (DVA) is reduced in the vertical plane at frequencies of 2 Hz and in the horizontal plane at frequencies of 0.8 Hz. DVA varies with target location, with acuity optimized for targets in the plane of motion. Thus, low frequency perturbations in horizontal and vertical planes can cause decrements in visual performance that may be exacerbated after long-duration spaceflight.

Goal 2: For determining efficacy of VSR stimulation on physiological and perceptual responses during otolith-canal conflicts and dynamic perturbations we have conducted the following series of studies: 1. We have shown that imperceptible binaural bipolar electrical stimulation of the vestibular system across the mastoids enhances balance performance in the mediolateral plane while standing on an unstable surface. We have followed up on the results of this previous study showing VSR stimulation improved balance performance in both mediolateral and anteroposterior planes while stimulating in the mediolateral axis only. 2. We have shown the efficacy of VSR stimulations on enhancing physiological and perceptual responses of whole-body orientation during low frequency perturbations (0.1 Hz) on the ocular motor system using a variable radius centrifuge (VRC) on both physiological (using eye movements) and perceptual responses (using a joystick) to track imposed oscillations. The variable radius centrifuge provides a selective tilting sensation that is detectable only by the otolith organs providing conflicting information from the canal organs of the vestibular system (intra-vestibular conflict). These results indicate that VSR can improve performance in sensory conflict scenarios like that experienced during spaceflight. 3. We have showed the efficacy of VSR stimulation to improved balance and locomotor control on subjects exposed to continuous, sinusoidal lateral motion of the support surface while walking on a treadmill while viewing perceptually matched linear optic flow. 4. We have developed and tested a practical methodology of finding the optimal amplitude of VSR stimulation using perceptual thresholds indicated by seated subjects using a game pad in response to applied electrical vestibular stimulation with sinusoidal signals of varying peak amplitudes. Preliminary analysis of these data indicated that the optimal amplitude of stimulation was found to be in the range of 10 to 20% of their maximum probability of detecting the signal. 5. We have developed a methodology to detect the functional vestibular cortex using a magnetic resonance imaging (MRI) compatible device and this study is ongoing to determine the effects of VSR stimulation on brain function. 6. We have shown the safety of short term continuous use of up to 4 hours of VSR stimulation and its efficacy in improving balance and locomotor function in Parkinsonian Disease patients. Thus, maximizing postural, locomotor, and perceptual performance during dynamic movements will have a significant impact on development of vestibular SR as a unique system to aid recovery of function in astronauts after long-duration spaceflight or in people with balance disorders.

The data obtained in this project will aid in the design of a countermeasure system used for improving functional tasks during and after g-transitions. The VSR methodology developed in the current project is being integrated with the sensorimotor adaptability (SA) training modalities being developed by Dr. Bloomberg and his team to improve its efficacy. The operational version of this countermeasure will be available as a skin patch vestibular prosthesis during spaceflight that will further act synergistically along with the pre-and in-flight SA training and provide an integrated, multi-disciplinary countermeasure capable of fulfilling multiple requirements making it a comprehensive and cost effective countermeasure approach.

Earth-Based Applications: VSR stimulation prostheses have Earthbound application in rehabilitation of patients with balance disorders, strokes, spinal cord injury, peripheral neuropathy in the legs or a single hand that has been injured, and low vision, and for fall prevention training among seniors. This project will also enhance the efficacy of ground-based rehabilitation and training programs.

1. Developed a practical methodology to determine optimal stimulation levels that will enable maximizing balance and locomotor task performances during task performance or training. This will enable ease of application of SR stimulation in practice. In order to improve the efficacy of implementation of this countermeasure a practical methodology to determine customized subject specific optimal amplitude if noise was needed to be implemented. Towards this goal we have developed and tested a practical methodology of finding the optimal amplitude of stimulation using perceptual thresholds indicated by seated subjects using the joystick on a game pad in response to applied electrical vestibular stimulation with sinusoidal signals of varying amplitudes. We mapped the optimal stimulation levels to the threshold curve obtained in previous experiments in which subjects performed both the balance and locomotor tasks and determined that the optimal levels of stimulation were in the range of 20-40% of threshold.

2. We examined how vestibular SR stimulation (VSR) affects measures of brain structure, functional network integrity, and vestibular function using Diffusion Tensor Imaging (DTI), Functional Connectivity MRI (magnetic resonance imaging), and Functional MRI. We have developed a methodology for using a MRI compatible tapper device which elicits vestibular evoked myogenic potentials (VEMPs). This device enables the mapping of the functional vestibular cortex. We are conducting a further validation study comparing functional MRI data in response to both the tapper device and to auditory tone bursts to map the functional vestibular cortex. We have collected data on 8 participants thus far, and the preliminary analyses reveal good correspondence in the activation patterns for the two methods. We will complete data collection on 15 participants and analyze the data for publication. We will then move on to image vestibular responses to the low level VSR stimulation.

3. We investigated the safety of use and possible effects of VSR alone and combined with L-DOPA in patients with Parkinsons Disease (PD). SVS (stochastic vestibular stimulation) or sham stimulation was administered to 10 PD patients in a double-blind placebo controlled cross-over pilot study. Motor symptoms and balance were evaluated in a defined off-medication state and after a 200 mg test dose of L-DOPA, using UPDRS-III, Posturo- Locomotor- Manual (PLM) movement times (MT), static posturography, and force plate measurements of the correcting response to a balance perturbation. Results suggest that short term use of SVS is safe, improves corrective postural responses, and has a small positive effect on motor symptoms in PD patients off treatment.

Movement Disorders 2014, Stockholm, Sweden June 8-12, 2014. , Jun-2014

35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society meeting, Osaka, Japan, July 3-7, 2013. , Jul-2013

Stochastic resonance (SR) is a mechanism whereby noise can assist and hence enhance the response of neural systems by detecting sub-threshold signals. SR thus enables the enhanced detection of relevant sensory signals. SR stimulation using imperceptible noisy vibratory or electrical stimulation has been shown to improve balance function in normal young and elderly subjects, stroke patients and in the rehabilitation of functional ankle joint instabilities. This project specifically has used imperceptible levels of electrical stimulation of the vestibular system (Vestibular SR/VSR) as the proposed countermeasure to improve performance in egress tasks. The project has also conducted a series of studies to document human visual performance during simulated low frequency dynamic perturbations and further investigate the efficacy of VSR stimulation on physiological and perceptual responses during otolith-canal conflicts and dynamic perturbations. The objective of two separate studies that were conducted was to document human visual performance during simulated low frequency vehicular motions.

In the first study we examined the changes in accuracy in normals when performing a seated visual target acquisition task in which the location of target was offset vertically during horizontal full-body rotation at an oscillating frequency of 0.8 Hz (peak velocity-160 deg/s). The main finding was that the accuracy of performance degraded by one step size and response times varied with target location when acquiring off-plane targets at perturbing frequencies of 0.8 Hz in the horizontal plane.

In the second study we examined 112 normals and 45 patients who had been diagnosed with either unilateral vestibular weaknesses or with post-acoustic neuroma resections. We determined their seated dynamic visual acuity (DVA) task performance while the chair was stationary and during vertical full-body oscillations at perturbing frequencies of 2 Hz (peak-to-peak motion of 5 cm). Scores were worse for both groups during the dynamic condition compared to the static condition. Further, in the dynamic condition patients' scores were significantly worse than normals' scores. These results indicate that low frequency perturbations in the horizontal and vertical planes can cause decrements in visual performance and can exacerbate sensorimotor deficits after spaceflight at low frequencies of dynamic movements.

We studied the efficacy of low imperceptible levels of stochastic electrical stimulation of the vestibular system in three separate studies

* In the first study VSR efficacy was evaluated during an otolith-canal conflict scenario in a variable radius centrifuge at low frequency of oscillation (0.1 Hz) on physiological responses (using eye movements) and perceptual responses (using a joystick) to track imposed oscillations. Results show that VSR stimulation significantly reduced the phase difference between both the eye counter roll movements as well as the perceptual tracking responses with respect to the imposed tilt in gravito-inertial vector. These results indicate that stochastic electrical stimulation of the vestibular system can improve otolith specific responses in intra-vestibular conflict scenarios like that experienced during spaceflight.

* In the second study VSR efficacy was evaluated on the cross-planar improvement in balance performance on an unstable surface while stimulating in the mediolateral (ML) axis only. Low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system improved cross-planar balance performance. The amplitude of optimal stimulus for improving balance performance was predominantly in the range of 30-210 µA RMS. These results indicate that bipolar binaural stimulation may be sufficient to provide a comprehensive countermeasure approach for improving postural stability.

* In the third study VSR efficacy was evaluated during locomotion on an unstable surface. Low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system improved locomotor performance consistent with the SR phenomenon in normal healthy subjects. These results indicate that VSR may be used to maximize locomotor performance during dynamic movements. The data obtained in this project will aid in the design of a countermeasure system used for improving functional tasks during and after g-transitions.

We have also been working with other PIs in the HRP and NSBRI Sensorimotor team. The VSR methodology developed in the current project is being integrated with the sensorimotor adaptability (SA) training modalities being developed by Dr. Bloomberg and his team to improve its efficacy. The operational version of this countermeasure will be available as a skin patch vestibular prosthesis during spaceflight that will further act synergistically along with the pre-and in-flight SA training and provide an integrated, multi-disciplinary countermeasure capable of fulfilling multiple requirements making it a comprehensive and cost effective countermeasure approach.

Earth-Based Applications: VSR stimulation prostheses have Earthbound application in rehabilitation of patients with balance disorders, strokes, spinal cord injury, peripheral neuropathy in the legs or a single hand that has been injured, and low vision, and for fall prevention training among seniors, as well as in both military and civilian occupations that involve shipping across oceans and flying in turbulence. This project will also enhance the efficacy of ground-based rehabilitation and training programs.

In the second study we examined 112 normals and 45 patients who had been diagnosed with either unilateral vestibular weaknesses or with post-acoustic neuroma resections. We determined their seated dynamic visual acuity (DVA) performance in stationary and during 5 cm vertical oscillations of 2 Hz.

Scores were worse for both groups during the dynamic condition vs. the static condition. Further, scores for patients were significantly worse than normals in the dynamic condition. These results indicate that low frequency perturbations in the horizontal and vertical planes can cause decrements in visual performance and can exacerbate sensorimotor deficits after space flight. We studied the efficacy of VSR stimulation in three separate studies – In the first study VSR efficacy was evaluated during an otolith-canal conflict scenario in a variable radius centrifuge at low frequency oscillation (0.1 Hz) on physiological (eye movements) and perceptual (joystick) responses. Results show that VSR stimulation significantly reduced the phase difference between both the eye counter roll movements as well as the perceptual tracking responses with respect to the imposed tilt in gravito-inertial vector. These results indicate that VSR can improve otolith specific responses in intra-vestibular conflict scenarios like that experienced during space flight. In the second study VSR efficacy was evaluated on the cross-planar improvement in balance performance on an unstable surface while stimulating in the mediolateral (ML) axis only. Low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system improved cross-planar balance performance. The amplitude of optimal stimulus for improving balance performance was predominantly in the range of 30-210 µA RMS. These results indicate that bipolar binaural stimulation may be sufficient to provide a comprehensive countermeasure approach for improving postural stability. In the third study VSR efficacy was evaluated during locomotion on an unstable surface. Low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system improved locomotor performance consistent with the SR phenomenon in normal healthy subjects. These results indicate that VSR may be used to maximize locomotor performance during dynamic movements.

Therefore, the overall goals of this project are to:

1) Investigate performance of motor and visual tasks during simulated varying sea state conditions with perturbations in the frequency range from 0.2-2.0 Hz.

2) Develop a countermeasure based on stochastic resonance that could be implemented to enhance sensorimotor capabilities with the aim of facilitating rapid adaptation to gravitational transitions following long-duration spaceflight.

The objective of two separate studies that were conducted was to document human visual performance during simulated wave motion in the 0.1 to 2.0 Hz range. In the first study we examined, in 12 healthy subjects, the changes in accuracy when performing a seated visual target acquisition task in which the location of target was offset vertically during horizontal full-body rotation at an oscillating frequency of 0.8 Hz (peak velocity of 160 deg/s). The main finding was that the accuracy of performance degraded in 7 of 12 subjects when acquiring vertical targets at perturbing frequencies of 0.8 Hz in the horizontal plane by one step size. In the second study we examined 112 normals and 45 patients who had been diagnosed with either unilateral vestibular weaknesses or with post-acoustic neuroma resections. Subjects sat in a chair that could oscillate vertically with the head either free or constrained with a cervical orthosis. We determined their seated dynamic visual acuity (DVA) task performance while the chair was stationary and during vertical full-body oscillations at perturbing frequencies of 2 Hz (peak-to-peak motion of 5 cm). Scores were worse for both groups during the dynamic condition compared to the static condition. In the dynamic condition patients's scores were significantly worse than normals's scores. Dynamic visual acuity (DVA) is reduced in the vertical plane at frequencies of 2 Hz and in the horizontal plane at frequencies of 0.8 Hz. DVA varies with target location, with acuity optimized for targets in the plane of motion. Thus, low frequency perturbations in the horizontal and vertical planes can cause decrements in visual performance. Perturbations at low frequency motions (0.1-2 Hz) may exacerbate sensorimotor deficits after spaceflight.

We have completed a study on the development of a countermeasure with the aim of facilitating rapid adaptation to gravitational transitions following long-duration spaceflight. Stochastic resonance (SR) is a mechanism by which noise can assist and enhance the response of neural systems to relevant sensory signals. Application of imperceptible SR noise coupled with sensory input through the proprioceptive, visual, or vestibular sensory system has been shown to improve motor function. Specifically, studies have shown that vestibular electrical stimulation by imperceptible stochastic noise (SRVS), when applied to normal young and elderly subjects, significantly improved their ocular stabilization reflexes in response to whole-body tilt as well as balance performance during postural disturbances. Our study showed that low imperceptible levels of white noise based electrical stimulation of the vestibular system improves balance performance consistent with the stochastic resonance phenomenon in normal healthy control subjects. The amplitude of optimal stimulus for improving balance performance was predominantly in the range of 100-400 µA. An SRVS based device may be fielded, either as a training modality to enhance adaptability or skill acquisition, or as a miniature patch type stimulator that may be worn by astronauts to enhance adaptation following gravitational transitions including people with disabilities due to aging or disease, improving posture and locomotion function.

2) Visual acuity was measured in 12 healthy subjects. Acuity thresholds were established using Landolt C optotypes presented on a LCD screen at 1.3 m. In dynamic tests chair oscillated at 0.8 Hz at peak velocity 60 deg/sec. All acuity measures were made using a forced-choice strategy. To measure the effect of target location optotypes were randomly presented at nine different locations on the screen offset upto 10 degrees. The optotype size was set to Snellen ratios of 20/20, 20/30 or 20/50. Presentation duration was set to 150, 300 and 450 ms. All these conditions were counterbalanced across 5 trials. Dynamic visual acuity threshold was reduced relative to static acuity in 7 of 12 subjects by one step size during horizontal rotational motion at 0.8 Hz. Both accuracy and reaction time varied as a function of target location, with greater performance decrements when acquiring vertical targets.

3) 15 subjects performed a standard balance task of standing on a block of foam with their eyes closed. Bipolar stochastic electrical stimulation was applied to the vestibular system using a constant current stimulator through electrodes placed over the mastoid process behind the ears. Amplitude of the signals varied in the range of 0-700 microamperes. Balance performance was measured using a force plate and inertial motion sensors placed on the trunk and head. Balance performance with stimulation was significantly improved in the range of 10%-25% compared with no stimulation. The signal amplitude at which performance was maximized was in the range of 100-400 microamperes. In the current year we are implementing studies to determine the efficacy of vestibular stochastic resonance in 1) physiological and perceptual responses under canal-otolith conflict perturbations using a Variable radius centrifuge 2) balance and locomotor performance on unstable platforms. Further we are investigating if we can predict the efficacy of the countermeasure using tests of sensory-preferences.

This project has resulted in 7 Abstracts presented at 4 different meetings, 2 Invention Disclosures, and 1 article in peer reviewed journals.

34th MidWinter Meeting of the Association for Research in Otolaryngology, Baltimore, MD, February 19-23, 2011. , Feb-2011

8th Symposium on the Role of the Vestibular Organs in Space, Houston, TX, April 8-10, 2011. , Apr-2011

Neuroscience 2010, Society for Neuroscience's 40th Annual Meeting, San Diego, CA, November 13-17, 2010. , Nov-2010

34th MidWinter Meeting of the Association for Research in Otolaryngology, Baltimore, MD, February 19-23, 2011. , Feb-2011

8th Symposium on the Role of the Vestibular Organs in Space, Houston, TX, April 8-10, 2011. , Apr-2011

8th Symposium on the Role of the Vestibular Organs in Space, Houston, TX, April 8-10, 2011. , Apr-2011

18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011. , Apr-2011

Therefore, the overall goals of this project are:

1) to investigate performance of motor and visual tasks during varying sea state conditions simulated using a six degree of freedom motion platform (6 DOFMP).

2) to develop a countermeasure based on stochastic resonance that could be implemented to enhance sensorimotor capabilities with the aim of facilitating rapid adaptation to gravitational transitions following long-duration spaceflight.

In the current year we are completing experiments investigating the robustness of balance performance responses to the countermeasure based on stochastic resonance. In the following year we are aiming to characterize performance on functional tasks using a 6DOFMP as a function of frequency and amplitude across different planes of motion and continue testing efficacy of the SR stimulation under otolith-canal mismatch conditions using off vertical axis rotation (OVAR) while seated in a chair.

Stochastic resonance (SR) is a mechanism by which noise can assist and enhance the response of neural systems to relevant sensory signals. Application of imperceptible SR noise coupled with sensory input through the proprioceptive, visual, or vestibular sensory system has been shown to improve motor function. Specifically, studies have shown that vestibular electrical stimulation by imperceptible stochastic noise (SRVS), when applied to normal young and elderly subjects, significantly improved their ocular stabilization reflexes in response to whole-body tilt as well as balance performance during postural disturbances. The goal of the study performed in the first year of the project was to 1) study the efficacy of SRVS on improving balance performance during standing on an unstable surface; 2) optimize the characteristics of the SRVS; and 3) determining the robustness of the balance performance responses to the SRVS.

Subjects performed a standardized balance task of standing on a block of 10-cm-thick medium-density foam with their eyes closed for a total of 43.5 seconds. Balance performance was measured using a force plate under the foam block and using inertial motion sensors placed on the torso and head segments. Stochastic electrical stimulation was applied to the vestibular system through electrodes placed over the mastoid process behind the ears. A new portable constant current stimulator driven by a microprocessor powered using a 3.7 V battery and capable of delivering ±5mA with subject isolation was designed and built to deliver the stimulus. Stochastic stimulation signals were generated with frequencies in the bandwidth of 1-2Hz and 0.01-30Hz. Subjects were tested at seven amplitudes of the signals, with the root mean square of the signal increasing by 30 microamperes for ±100 µA increment in the current range of 0 µA - ±700 µA. Six parameters were calculated to characterize the performance of subjects during the baseline (first half of a trial) and the stimulus (latter half of trial) periods for all seven amplitudes: RMS of - medial-lateral (ML) force; roll moment; ML linear acceleration and roll angular velocity for head and torso segments. Optimal stimulus amplitude was determined as the one at which the ratio of parameters from the stimulus period to the baseline period for any amplitude range was less than that for the no stimulus condition (0 µA) on a minimum of four of six parameters listed above.

Balance performance showed significant improvement with the application of the vestibular SR stimulation in the range of 10%-25% in 10 out of 15 subjects compared with 5%-26% in 8 out of 15 subjects for the 0-30Hz and 1-2Hz frequency ranges, respectively, across all six parameters. The amplitude levels at which subjects showed the optimal improvement in performance was varied across subjects and different for the two frequency ranges even for the same subjects. Optimization of the frequency and amplitude of the stochastic noise signals for maximizing balance performance will have a significant impact on development of vestibular stochastic resonance as a unique system to aid recovery of function in astronauts after long-duration spaceflight or in people with balance disorders.

In the current year we are continuing to implement the second half of the study investigating the robustness of the SR responses by testing the reproducibility of the results under similar task conditions; while simultaneously performing a cognitive task (auditory stroop test) and under a novel unstable condition while performing a fine motor control task (Force control).

Aviation, Space, and Environmental Medicine 2010 Mar;81(3):216. , Mar-2010

NASA Human Research Program Investigators' Workshop, Houston, TX, Abstract Book, February 2010. , Feb-2010

The act of emergency egress includes and is not limited to rapid motor control tasks -- including both fine motor control such as object manipulation and gross motor control such as opening a hatch -- and visual acuity tasks while maintaining spatial orientation and postural stability in time to escape safely. Exposure to even low frequency motions (0.2-2.0 Hz) induced by sea conditions surrounding a vessel can cause significant fine and gross motor control problems affecting critical functions. These motion frequencies coupled with the varying sea-state conditions (sea states 1-7 indicate frequencies ranging from 0.125-0.5 Hz) cause performance deficits by affecting the efficacy of motor and visual-acuity-dependent skills in tasks critical to emergency egress activities, such as visual monitoring of displays, actuating discrete controls, operating auxiliary equipment, and communicating with Mission Control and recovery teams. Thus, during exploration-class missions, the sensorimotor disturbances due to the crewmember's adaptation to microgravity may lead to disruption in the ability to maintain postural stability and perform functional egress tasks during the initial introduction to the Earth's gravitational environment.

At present, the functional implication of the interactions between a debilitated crewmember during readaptation to Earths gravity and the environmental constraints imposed by a water landing scenario is not defined and no operational countermeasure has been implemented to mitigate this risk. Stochastic resonance (SR) is a mechanism whereby noise can assist and enhance the response of neural systems to relevant, subthreshold sensory signals. Application of subthreshold stochastic resonance noise coupled to sensory input through the proprioceptive, visual or vestibular-sensory systems has been shown to improve motor function. Crew members who have adapted to microgravity have acquired new sensorimotor strategies that take time to discard.

We hypothesize that detection of time-critical subthreshold sensory signals will play a crucial role in improving strategic responses. Thus, the rate of skill re-acquisition will be faster, leading to faster recovery of function during their re-adaptation to Earth's gravity. Therefore, we expect the use of stochastic resonance mechanisms will enhance the acquisition of new strategic abilities. This process should ensure rapid restoration of functional egress capabilities during the initial return to Earths gravity after prolonged spaceflight.

Specific Aims

1) Investigate performance of motor and visual tasks during varying sea-state conditions.

2) Develop a countermeasure based on stochastic resonance that could be implemented to enhance sensorimotor capabilities with the aim of facilitating rapid adaptation to Earth's gravity, allowing rapid vehicle egress on water in varying sea states following long-duration spaceflight.