This project innovates upon two patented technologies developed from principal investigator (PI) Michael Schubert and co-investigator Americo Migliaccio (US20100198104 and US20160242642A1, https://www.uspto.gov ), by refining users' ability to self-treat motion sickness. The device we have built for use in this project guides users to perform sinusoidal head rotations, matched to a metronome, about the yaw, pitch, and roll axes (90 sec epochs, 5 minutes per axis, 15 min total). In addition, the device includes the capacity for a subject to rate his/her/their perception of motion sickness using a handheld controller and integrates a heart-rate monitor worn over the subject's arm. Video-oculography captures eye and head velocity, and also tracks the number of blinks and heart rate variability – metrics that can indicate worsening nausea.

The benefits of this research to life are similar and critical in both space and Earth environs – validation of an autonomous treatment for motion sickness and balance disorders.

At the Naval Medical Research Unit Dayton (NAMRU-D), we are using the Disorientation Research Device (DRD) and have conducted two "dry-runs" for 1 hour each, exposing subjects to 60 minutes of rotation at 2.5Gx. The dry-runs have been critical to ensure the safety and comfort of the subjects, ensuring the DRD motion profile is effectively generating motion sickness similar to what crew members experience on long-duration space travel, delivery of equipment, and training of the NAMRU-D personnel in proper use of the equipment for independent data collection. A final dry-run is scheduled for January 2024. In addition to the same outcome measures listed for the JHU site, we will also collect video ocular counter roll (vOCR) data. The vOCR data collection is enabled from a NASA Human Research Program (HRP) augmentation grant award (Colin Grove) to the PI (Schubert). The vOCR measures degrees of ocular roll that will be compared between groups and correlated with our outcome measures. Of interest will be to compare vOCR data with subject perception of motion sickness, which prior literature has suggested may predict those crewmembers warranting a rehabilitative countermeasure as intervention.

Each site will randomize a total of n=24 subjects to participate in either the traditional means for treating motion sickness (rest at NAMRU-D; vestibular rehabilitation at JHU) or the StableEyes With Active Neurofeedback (SWAN) self-administered rehabilitation method.

Preliminary Results suggest: 1. Pre-operative asymmetry exists in the perception of oculomotor alignment. 2. Asymmetries of vertical misalignment improve, but asymmetry in torsional alignment persists. 3. Both traditional and SWAN rehabilitation appear to similarly mitigate the significant decrease in accuracy as patients recover over 2 weeks. 4. Compared to traditional rehabilitation, subjects who participated in the SWAN rehab (the self-administered rehabilitation) completed the "Timed Up and Go" Test more quickly at 2 weeks post-op and with a larger improvement. 5. Compared to traditional rehabilitation, subjects who participated in the SWAN rehab had larger improvements in duration to stand on firm or foam surfaces with eyes open or closed. 6. Compared to traditional rehabilitation, subjects who participated in the SWAN rehab had larger improvements in duration to stand on firm or foam surfaces with eyes open or closed on foam with their heads extended.

We delivered two poster presentations at the 2023 NASA Human Research Program Investigators’ Workshop (IWS). For the 2024 IWS, we have submitted three abstracts for presentation. One paper establishing the video-oculographic functionality used in the SWAN device has been published.

The benefits of this research to life are similar and critical in both space and Earth environs – validation of an autonomous treatment for motion sickness and balance disorders.

This project innovates on the well-established, yet novel, incremental vestibulo-ocular reflex (VOR) rehabilitation training device (StableEyes, Todd et al., 2018; Rinaudo et al., 2021; Rinaudo et al., 2021a) in two primary ways: first, we have developed video-oculography (VOG) and related software that can identify the physiologic mechanisms responsible for the behavior change we intend. We call the rehabilitation training device with VOG capability the StableEyes with Active Neurofeedback (SWAN) device. The SWAN device with rehabilitation method has been validated in a recent publication (Todd et al., 2022). Next, we have innovated on the self-administered rehabilitation method by developing a paradigm that reinforces active head movement at amplitudes above therapeutic thresholds but below aversive thresholds. We have thus modified the incremental VOR rehabilitation method to train gradual increase in head amplitude as an attempt to mitigate gravitation transition (G-transition)-induced motion sickness and optimize crew performance.

Our progress over the 2nd year of this award is as follows:

I. Development of the SWAN Device (hardware and software): We have built four complete VOG and behavioral testing devices (hardware and software) to a point of operation and have tested the suite of oculomotor tests that include smooth pursuit, saccades, and video head impulse – known to be abnormal during motion sickness. Each of the four units are operational. Part of this development included creating our unique version of eye tracking, which includes a calibration routine, to ensure adjustment of the pupil size and proper fit of the goggles over the face.

The rehabilitation module guides and monitors self-generated yaw, pitch, and roll head rotations over three epochs of five minutes each. During rehabilitation, SWAN monitors blinks, heart rate, eye and head velocity, and quality of head motion, while subjects input symptom intensity changes on a hand-held device that can then be used to adjust subsequent head movement amplitude. Visual feedback is provided to guide desired head motion. We have created an operations manual for the SWAN device.

II. Development of the Motion Sickness Treatment Protocol and Data Intake Forms: The Motion Sickness Treatment Protocol (incremental head amplitude) has been finalized. We have created a single data intake sheet to be used for both objectives (data collected in civilians undergoing vestibular nerve resection and healthy subjects exposed to centrifugation).

III. Development of the Motion Sickness Centrifugation Protocol (including the cabin specifications): To date we have determined our acceleration profile, subject positioning within the centrifuge, and how to monitor spontaneous head and trunk movements during the centrifugation.

IV. Augmentation Award: With support from an augmentation award in February of 2022, we will correlate motion sickness with ocular counter roll and perception of visual vertical. To date, we have purchased the necessary VOG equipment to measure ocular counter roll, built the visual perceptual software, and finalized the data collection protocol.

The benefits of this research to life are similar and critical in both space and Earth environs – validation of an autonomous treatment for motion sickness and balance disorders.

To date, we have secured a reliance agreement between NASA and Johns Hopkins University (JHU) that allows JHU to serve as the single Institutional Review Board (IRB) of record for the study. We have an approved IRB protocol to begin data collection at JHU for objective 1 (reduce motion sickness in civilians with vestibular nerve surgical ablation). We are working with Wright-Patterson Air Force Base (Dayton, OH) to secure local IRB approval to begin data collection on objective 2 (reduce motion sickness in healthy controls exposed to centrifugation using the Disorientation Research Device). We have submitted final paperwork to secure the data share agreement (Cooperative Research and. Development Agreement or "CRADA") between JHU and Wright-Patterson Air Force Base.

Both the principal investigator (Michael Schubert), two co-investigators (Americo Migliaccio and Scott Wood), and a post-doctoral fellow have met biweekly during the year to develop the motion profile we will use in attempt to reduce motion sickness and improve balance. The motion profile will task users to perform sinusoidal head rotations, matched to a metronome, about the yaw, pitch, and roll axes (90 sec epochs, 5 minutes per axis, 15 min total). The assessment for each axis consists of the number of completed epochs, with each epoch requiring head rotations of a different frequency/amplitude/velocity. Subjects are instructed to begin with an ‘easy’ amplitude (i.e., small) and increase or decrease amplitude depending on their perception of motion sickness – which is input from 0 (absent motion sickness) to 10 (vomit) using a handheld controller. Video-oculography captures eye and head velocity; it also tracks the number of blinks and saccades, metrics that can indicate worsening nausea.

Both objective 1 and 2 incorporate use of a rehabilitation device (patented) that uses video-oculography and provides auditory feedback for automated vestibular rehabilitation. The device will be innovated upon and built by the laboratory of Americo Migliaccio, in Sydney, Australia. Unfortunately, due to the outbreak of the COVID-19 Delta strain, the City of Sydney, Australia enforced a mandatory lockdown beginning June 26, 2021. In addition to the shutdown, the worldwide supply chain shortage of electronics has limited our ability to build the intended four devices. As a result, we remain at least six months behind schedule; that will impact our ability to complete objective 1 as originally intended.

As mitigation, we are working hard to build three devices (not four) using parts salvaged from prototypes. We are hopeful to have the three devices built, tested for functionality, and delivered to the U.S. within the next four months. This ten-month delay is preventing data collection for objective 1 and 2. Given the delay, we will not conduct a clinical trial at the JHU site that was to compare outcome measures between traditional vestibular rehabilitation and the novel rehabilitation device. Instead, we will conduct an observational study that examines how well the device improves performance and is adopted by the patient subjects. This mitigation is a feasible step necessary to enable useful data for both the civilian and NASA objectives within the remaining two years of the study.