NOTE: End date changed to 4/30/2024 per V. Lehman/JSC (Ed., 5/16/23)

NOTE: End date changed to 4/30/2023 per NSSC information (Ed., 5/2/22)

NOTE: End date changed to 4/30/2022 per NSSC information (Ed., 4/12/21)

NOTE: End date changed to 4/30/2021 per NSSC information (Ed., 5/4/2020)

NOTE: Changed end date to 9/30/2020 per L. Juliette/HRP (Ed., 2/19/2020)

NOTE: Extended to 1/31/2020 per K. Ohnesorge/HRP JSC (Ed., 5/24/18)

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group developed ROBoT for research use (ROBoT-r) and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT-r and NINscan-SE were deployed during the Human Exploration Research Analog (HERA) Campaigns 4 and 5. We will deployed both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we recruited 36 crewmembers from nine 45-day missions in the HERA facility during Campaigns 4 and 5, plus 24 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2-3x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We also worked with the Human Factors and Behavioral Performance (HFBP) Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. A sleep restriction intervention was included in HERA C4. In addition, CMs included a lighting intervention, a diet intervention, and a habitat (volume and privacy) intervention. We tested hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We also compared ROBoT performance to the standardized Cognition Test Battery.

The knowledge-deliverables of this project include: (i) changes in operationally-relevant (ROBoT-r) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT-r performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS (near-infrared spectroscopy), EEG, or polysomnography device has both the portability and the multi-use features of the system we deployed. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

Summary and Takeaways

While we strongly encourage the reader to review the entire report to understand our results and statements in proper context, here we list some key points from across this project that we consider particularly important to highlight.

Aim 1: Characterize operationally-relevant task performance changes during 45-day HERA missions. We thoroughly characterized operationally-relevant task performance changes associated with 45-day HERA missions across numerous behavioral metrics. With regard to our specific hypotheses: • Hypothesis 1.1: Overall ROBoT-r performance in HERA crewmembers will differ significantly from controls, and will be related to time-in-mission. o We found that being in HERA sequestration led to poorer performance on ROBoT-r, and that there was a significant improvement in performance over time-in-mission, driven by a strong learning curve that lasted through the majority of the HERA sequestration period. • Hypothesis 1.3: Overall ROBoT-r performance will be significantly poorer during emergency procedures than during ordinary ROBoT performance. o Contrary to our hypothesis, when comparing apples-to-apples (i.e., 100% difficulty trials, which were the only type of trials conducted on emergency days), we unexpectedly found performance during emergency procedures to be equivalent to behavioral performance on adjacent days. So, despite the high difficulty and the unscheduled nature of emergency trials, participants were able to handle those without performance reductions. We, therefore, ignored these sessions in following analyses.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions. We also thoroughly characterized a number of systemic physiology and brain changes during the 45-day HERA missions. With regard to our specific hypotheses: • Hypothesis 2.1: NIRS measures of prefrontal cortical activity during the ROBoT task will vary as a function of time-in-mission and sleep debt. o Time-in-Mission  Resting HRV increased; whereas, during ROBoT-r HRV increased and the following all decreased: HRslope, Pcardiac, Presp, and L-DLPFC, Fp1, and Fp2 activation levels. o Sleep Restriction  HR during ROBoT-r tasks was elevated with sleep restriction

Aim 3: Identify physiological or behavioral variables that predict operational performance. Since the Cognition Test Battery (CTB) and ROBoT-r were often conducted on the same day, we used Cognition outcome metrics to predict ROBoT-r performance. We identified four tests within the CTB whose outcome metrics provided predictive value for ROBoT-r weighted_scores: Abstract Matching, Motor Praxis Test, Emotion Recognition, and the Line Orientation Test. • Hypothesis 3.1: One or more physiological variables will exhibit significant relationships with overall performance on ROBoT-r trials. o We investigated whether EEG power spectra in the rest period could predict subsequent ROBoT-r performance, but found no significant relationships. We did find significant relationships with ROBoT-r (in the theta and alpha bands) during task performance, although those relationships would not be useful for predicting future performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures. While we did not implement any countermeasures of our own in this study, HERA C4/C5 included one major intervention (Sleep Restriction) and three separate countermeasures (Lighting, Diet, and Habitat Size). As discussed, we were unable to investigate Habitat Size. However, we were able to test for the effects of Lighting and Diet interventions. The experimental Lighting condition improved ROBoT-r performance (weighted_score and overall_success, with no effect on duration), largely counteracting the detrimental effects of Sleep Restriction. Diet did not significantly affect ROBoT-r performance overall, which is encouraging.

BRAIN-STIM Aim: Test whether transcranial electrical stimulation can improve ROBoT-r performance, as a potential spaceflight countermeasure. We conducted a thoroughly double-blind, sham-controlled study of brain stimulation over the L-DLPFC and the L-aINS in n=40 participants. • Hypothesis S1: tDCS will enhance performance on ROBoT-r compared to sham stimulation. o Contrary to our hypothesis, tDCS did not enhance performance and, in fact, had a small but statistically significant negative influence on ROBoT-r performance variables. While this was an unexpected result, and various explanations remain to be tested, we suspect the reason lies partly in the complex nature of the ROBoT-r task—which engages many brain regions simultaneously—and the rather large brain regions stimulated by tDCS.

Additional Key Details Here, we list some key details from across this project that we consider important to highlight.

ROBoT-R: • Isolation: There was a significant decrease in performance (poorer accuracy and lower probability of success) when participants were sequestered in HERA versus when they were outside of HERA (pre-/post-mission). • Lighting: The experimental lighting condition in HERA C4 significantly increased accuracy (Weighted Score), did not change speed (Duration), and significantly increased (near doubling) of the probability of overall success compared to control lighting. This highlights the role of sleep in behavioral performance and suggests that the dynamic lighting countermeasure (implemented by Dr. Steven Lockley) was a highly effective modulator of ROBoT-r performance. • Early Performance Disruptions: During the first two weeks after ICE ingress, there appeared to be a slowed learning process, with less improvement in accuracy or overall success and no improvement in speed compared to Controls. This could be related to the elevated stress, workload, sleep restriction, or more general “orientation” required upon entering a dramatically new environment. This is consistent with spaceflight reports of impaired performance and added workload/distraction in the days before and after both launch and landing. • ROBoT-r Control: Users of ROBoT seem to emphasize correcting translational error over rotational error, suggesting a different strategic control approach for the two hands. It also suggests that the lesser-attended modality—rotation—is likely to provide a more sensitive indicator of performance status. • Reversals and Collisions: Learning to avoid reversals and collisions seemed to occur more rapidly than for other metrics, plateauing after ~10 sessions as compared to the plateau after ~17 sessions for other variables. • C5 Scoring: The change in scoring of ROBoT-r between HERA C4 and C5 means that the training process for C5 (using the identical video and trainer guidance) was, in fact, inaccurate. Participants were told that reversals mattered and efficiency (=run duration) did not matter; whereas, the opposite was the case throughout C5. Moreover, merging efficiency(=duration) into weighted_score as of 2021 is particularly concerning, given that this fails to maintain a separation of accuracy from speed measures. As we understand it, this problem may still persist and is basically invisible to nearly all researchers. Our approach was to recompute weighted_score so that it was computed consistently throughout this study (2017-2024).

Physiology: • Brain Activation: In L-DLPFC, Fp2, and R-DLPFC exhibited significantly lower [HbD] changes, while in HERA, suggesting lower brain activation in this region while sequestered. This effect was almost completely compensated for by the Lighting intervention (both effect sizes ~5 M). • Cerebrovascular Pulsatility: While the meaning of cerebrovascular pulsatility changes is not yet fully understood, we did identify notably consistent responses across the different types of pulsatility: decreases with Mission Day, increases with Difficulty, and decreases in HERA, with sleep restriction, and with the Lighting and Diet countermeasures. This consistency merits further investigation.

BRAIN-STIM: Complex Tasks: The simple application of tES during a complex task such as ROBoT-r may not produce effects similar to those observed with simpler tasks. Given the distributed nature of tES stimulation in the brain, it will be important to conduct studies with the specific tasks to confirm and quantify relevant behavioral effects.

NOTE: End date changed to 4/30/2024 per V. Lehman/JSC (Ed., 5/16/23)

NOTE: End date changed to 4/30/2023 per NSSC information (Ed., 5/2/22)

NOTE: End date changed to 4/30/2022 per NSSC information (Ed., 4/12/21)

NOTE: End date changed to 4/30/2021 per NSSC information (Ed., 5/4/2020)

NOTE: Changed end date to 9/30/2020 per L. Juliette/HRP (Ed., 2/19/2020)

NOTE: Extended to 1/31/2020 per K. Ohnesorge/HRP JSC (Ed., 5/24/18)

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) C4 and C5 campaigns. In this project, we will deploy both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus up to 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) [Ed. note: Element is now known as Human Factors and Behavioral Performance] Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if possible.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS (near-infrared spectroscopy), EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

Progress over the past year is detailed below.

HERA Controls Data Collection: Having completed n=36 subjects from HERA Campaigns 4 and 5, the primary task over the past year has been to recruit and run control subjects to match the HERA participants. To date, we have completed running n=24 control subjects, with recruitment remaining slow (for a 9-week, 26-session experiment) but ongoing.

HERA Data Analysis: To date, all analyses remain preliminary, given the ongoing recruitment of control subjects. However, a number of features have been clearly identified.

• Weighted scores improve steadily and significantly throughout the ~60-day pre-, during- and post-HERA periods, representing improved accuracy at point of contact between Canadarm2 and the HTV-II vehicle. The proportion of successful captures also increases over this period.

• Time required to complete vehicle capture decreases steadily and significantly over this same period. Increased speed combined with the improved performance is a hallmark of learning, which appears to continue throughout the 60-day period (which represent ~10-12 hours of hands-on ROBoT-r performance).

• Performance is significantly affected by run difficulty, with each step-up in difficulty resulting in significantly poorer and slower performance.

• There were significant differences in overall performance levels across the different missions/crews, although some of these may have been influenced by changes in the HERA habitat.

• Preliminary behavioral results suggest that certain Cognition battery test scores can help predict ROBoT-r performance.

• Preliminary physiological data from NINscan demonstrate significant differences between HERA crews and controls in heart rate (HERA>Controls). Both groups exhibited changes in heart rate, as well as frontal pole and dorsolateral prefrontal brain activation within runs, suggesting progressive brain activation as the more challenging end-of-run phase approached.

• HERAnauts, in contrast to the non-isolated control group, exhibited no ROBoT-r performance improvement in Weighted Score or Overall Success (Fig C), nor did they perform the ROBoT-r task significantly faster during this same period compared to the Control group. HERAnauts did “catch up" on all measures by later in the mission (days 16-45).

In addition to the above findings, we have conducted analyses to examine the effects of the countermeasures (CMs) deployed in HERA Campaign 4. These analyses suggest the following:

• Confinement in HERA led to a significant performance impairment, equivalent to an increase in task difficulty of approximately 30%.

• The dynamic lighting schedule—with enriched blue light in the morning and enriched red light in the evening (as compared to standard lighting)—mitigated the majority of the performance deficit associated with confinement in HERA.

• The experimental diet—which included a 25% enrichment of omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables—had no significant improvements nor decrements on ROBoT-r performance.

Once all physiological datasets have been fully cleaned and preprocessed, we will conduct final statistical modeling to address our three physiologically related specific aims: (Aim 2) characterize brain and systemic physiology changes during HERA missions, (Aim 3) identify predictive brain and systemic physiological biomarkers for ROBoT-r performance, and (Aim 4) quantify the influence of behavioral health countermeasures on (neuro)physiological measures.

Dissemination: The latest findings from this study were presented at the Human Research Program (HRP) Investigators' Workshop (IWS) conference in Feb 2024. One peer-reviewed paper has been published. A second manuscript that examines the effects of countermeasures in HERA C4, and a third manuscript looking at the ability to predict ROBoT-r performance from Cognition scores are currently under final author review.

Supplement: This project includes a supplement to investigate the role of transcranial electrical stimulation (tES) on ROBoT-r performance, both acutely and over the 2 days immediately following stimulation. Data collection for the double-blind crossover design experiment is underway and is currently 75% complete.

NOTE: End date changed to 4/30/2023 per NSSC information (Ed., 5/2/22)

NOTE: End date changed to 4/30/2022 per NSSC information (Ed., 4/12/21)

NOTE: End date changed to 4/30/2021 per NSSC information (Ed., 5/4/2020)

NOTE: Changed end date to 9/30/2020 per L. Juliette/HRP (Ed., 2/19/2020)

NOTE: Extended to 1/31/2020 per K. Ohnesorge/HRP JSC (Ed., 5/24/18)

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) C4 and C5 campaigns. In this project, we will deploy both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus up to 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) [Ed. note: Element is now known as Human Factors and Behavioral Performance] Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if possible.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS (near-infrared spectroscopy), EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

Progress over the past year is detailed below.

HERA Data Collection: Having completed n=36 subjects from HERA Campaigns 4 and 5, the primary task over the past year has been to recruit and run control subjects to match the HERA participants. To date, we have completed running n=24 control subjects, with recruitment remaining slow (for a 9-week, 26-session experiment) but ongoing.

HERA Data Analysis: To date, all analyses remain preliminary, given the ongoing recruitment of control subjects. However, a number of features have been clearly identified. • Weighted scores improve steadily and significantly throughout the ~60-day pre-, during-, and post-HERA periods, representing improved accuracy at the point of contact between Canadarm2 and the HTV-II vehicle. The proportion of successful captures also increases over this period.

• Time required to complete vehicle capture decreases steadily and significantly over this same period. Increased speed combined with improved performance is a hallmark of learning, which appears to continue throughout the 60-day period (which represents ~10-12 hours of hands-on ROBoT-r performance).

• Performance is significantly affected by run difficulty, with each step-up in difficulty resulting in significantly poorer and slower performance.

• There were significant differences in overall performance levels across the different missions/crews.

• Preliminary physiological data from NINscan demonstrate significant differences between HERA crews and controls in heart rate (HERA>Controls). Both groups exhibited changes in heart rate, as well as frontal pole and dorsolateral prefrontal brain activation within runs, suggesting progressive brain activation as the more challenging end-of-run phase approached.

In addition to the above findings, we have conducted analyses to examine the effects of the countermeasures (CMs) deployed in HERA Campaign 4. These analyses suggest the following: • Confinement in HERA led to a significant performance impairment, equivalent to an increase in task difficulty of approximately 30%.

• The dynamic lighting schedule—with enriched blue light in the morning and enriched red light in the evening (as compared to standard lighting)—mitigated the majority of the performance deficit associated with confinement in HERA.

• The experimental diet—which included a 25% enrichment of omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables—had no significant improvements nor decrements in ROBoT-r performance.

Once all physiological datasets have been fully cleaned and preprocessed, we will conduct final statistical modeling to address our three physiologically related specific aims: (Aim 2) characterize brain and systemic physiology changes during HERA missions, (Aim 3) identify predictive brain and systemic physiological biomarkers for ROBoT-r performance, and (Aim 4) quantify the influence of behavioral health countermeasures on (neuro)physiological measures.

Dissemination: The findings to date from this study were presented at the virtual Human Research Program (HRP) Investigators' Workshop (IWS) conference in early February 2023. One peer reviewed paper has been published. A second manuscript that examines the effects of countermeasures in HERA C4 is scheduled to be submitted for peer-review soon. A third manuscript looking at the ability to predict ROBoT-r performance from Cognition scores is currently under author review.

Supplement: This project includes a supplement to investigate the role of transcranial electrical stimulation (tES) on ROBoT-r performance, both acutely and over the 2 days immediately following stimulation. This double-blind crossover design experiment is currently underway, approaching 50% complete.

NOTE: End date changed to 4/30/2022 per NSSC information (Ed., 4/12/21)

NOTE: End date changed to 4/30/2021 per NSSC information (Ed., 5/4/2020)

NOTE: Changed end date to 9/30/2020 per L. Juliette/HRP (Ed., 2/19/2020)

NOTE: Extended to 1/31/2020 per K. Ohnesorge/HRP JSC (Ed., 5/24/18)

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) C4 and C5 campaigns. In this project, we will deploy both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus up to 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) [Ed. note: Element is now known as Human Factors and Behavioral Performance] Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if possible.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS (near-infrared spectroscopy), EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

In the past year, the following tasks have been completed.

HERA Data Collection: Having completed n=36 subjects from HERA Campaigns 4 and 5, the primary task over the past year has been to recruit and run control subjects to match the HERA participants. COVID-19 restrictions and infections have continued to slow our data collection efforts, due to either resistance to participation or dropouts due to illness during the 9-week, 26-session experimental periods. To date, we have completed running n=14 control subjects, with additional subjects in process. To date, n=6 subjects have needed to discontinue related to COVID-19.

HERA Data Analysis: To date, all analyses remain preliminary, given the ongoing recruitment of control subjects. However, a number of features have been clearly identified.

• Weighted scores improve steadily and significantly throughout the ~60-day pre-, during- and post-HERA periods, representing improved accuracy at point of contact between Canadarm2 and the HTV-II vehicle. The proportion of successful captures also increases over this period.

• Duration to complete vehicle capture decreases steadily and significantly over this same period. Increased speed combined with the improved performance is a hallmark of learning, which appears to continue throughout the 60-day period (which represent ~10-12 hours of hands-on ROBoT-r performance).

• Performance is significantly affected by run difficulty, with each step-up in difficulty resulting in significantly poorer and slower performance.

• There were significant differences in overall performance levels across the different missions/crews.

• Preliminary physiological data from NINscan demonstrated significant differences between HERA crews and controls in heart rate (HERA>Controls). Both groups exhibited changes in heart rate, as well as frontal pole and dorsolateral prefrontal brain activation within runs, suggesting progressive brain activation as the more challenging end-of-run phase approached.

In addition to the above findings, we have conducted analyses to examine the effects of the countermeasures (CMs) deployed in HERA Campaign 4 (C4). These analyses suggest the following:

• Confinement in HERA led to a significant performance impairment, equivalent to an increase in task difficulty of approximately 30%.

• The dynamic lighting schedule – with enriched blue light in the morning and enriched red light in the evening (as compared to standard lighting) – mitigated the majority of the performance deficit associated with confinement in HERA.

• The experimental diet – which included a 25% enrichment of omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables – led to no significant improvements nor decrements in ROBoT-r performance.

Once all physiological datasets have been fully cleaned and preprocessed, we will conduct final statistical modeling to address our three physiologically-related specific aims: (Aim 2) characterize brain and systemic physiology changes during HERA missions, (Aim 3) identify predictive brain and systemic physiological biomarkers for ROBoT-r performance, and (Aim 4) quantify the influence of behavioral health countermeasures on (neuro)physiological measures.

Dissemination: The findings-to-date from this study were presented at the virtual NASA Human Research Program (HRP) Investigators' Workshop (IWS) in early February 2022. Portions of this effort were included in the Master’s Thesis of Dr. Stijn Thoolen at Kings College, London, and one peer-reviewed paper has been published. A second manuscript that examines the effects of countermeasures in HERA C4 is scheduled to be submitted for peer review soon.

Remainder of Year 6: In the remaining 2 months of grant year 6 we anticipate completing the following activities:

1) Data Collection: We will continue to pursue control subject recruitment and data collection, given that there are relatively few COVID-19 restrictions on research and masking at this time.

2) Data Quality Control: We will conduct a detailed data quality control assessment for all C4 and C5 datasets, building a complete, standardized dataset for delivery to NASA. This process will include identifying all anomalies (missing data, brief dropout, noise bursts, erroneous values, etc.) in all datasets so that analysis programs can be robust to such data features.

Manuscript Submission: We plan to submit our countermeasures paper based on HERA C4 data in the final two months of this grant year.

NOTE: End date changed to 4/30/2022 per NSSC information (Ed., 4/12/21)

NOTE: End date changed to 4/30/2021 per NSSC information (Ed., 5/4/2020)

NOTE: Changed end date to 9/30/2020 per L. Juliette/HRP (Ed., 2/19/2020)

NOTE: Extended to 1/31/2020 per K. Ohnesorge/HRP JSC (Ed., 5/24/18)

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) C4 and C5 campaigns. In this project, we will deploy both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus up to 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) [Ed. note: Element is now known as Human Factors and Behavioral Performance] Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if possible.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS (near-infrared spectroscopy), EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

In Years 4-5 of this project, the following tasks have been completed.

HERA Data Collection: In the past year, we completed data collection for the remainder of HERA Campaign 5, with the final subjects existing HERA just prior the imposition of COVID-19 lockdown restrictions in March 2020. This completed the in-HERA data collections (C4 and C5) for the project. When not under lockdown, we continued to recruit HERA control subjects to match the HERA participants. To date we have completed running n=10 subjects, with two subjects needing to be aborted related to COVID-19.

HERA Data Analysis: To date, all analyses remain preliminary, given the ongoing recruitment of control subjects. However, a number of features have been clearly identified.

• Weighted scores increase steadily and significantly throughout the ~60-day pre-, during-, and post-HERA periods, representing improved accuracy at point of contact between Canadarm2 and the HTV-II vehicle. The proportion of successful captures also increases over this period.

• Duration to complete vehicle capture decreases steadily and significantly over this same period. Increased speed combined with the improved performance is a hallmark of learning, which appears to continue throughout the 60-day missions (which represent ~10-12 hours of hands-on ROBoT-r performance).

• Performance is significantly affected by run difficulty, with each step-up in difficulty resulting in significantly poorer and slower performance.

• There were notable and significant differences in performance across the different missions/crews.

• Physiological data from NINscan demonstrated significant differences between HERA crews and controls in heart rate (HERA>Controls). Both groups exhibited changes in heart rate, as well as frontal pole and dorsolateral prefrontal brain activation within runs, suggesting progressive “activation” as the more challenging end of the run approached.

We are still finalizing dataset cleaning and preparing our analyses. Once complete, we will conduct statistical modeling to address our three specific aims: (1) characterizing changes in ROBoT-r performance in HERA, (2) characterizing brain and systemic physiology changes during HERA missions, and (3) identifying predictive brain and systemic physiological biomarkers for ROBoT-r performance.

Given the limited number of controls, we cannot yet assess whether or not there are firm conclusions regarding differences between HERA crewmembers and controls, for either behavioral performance or for physiological variables.

Dissemination: The results to date of ROBoT-r data collection were presented at the Human Research Program Investigators' Workshop (HRP IWS) conference in Galveston, TX in late Jan 2020, and additional findings at the virtual HRP IWS meeting in early Feb 2021. Portions of this effort were included in the Master’s Thesis of Dr. Stijn Thoolen at Kings College, London, and one peer reviewed paper has been published.

Remainder of Year 5: In the remaining 2 months of grant year 5 we anticipate completing the following activities:

Data Collection: We plan to ramp-up the HERA control recruitment and data collection, given the rapid loosening of COVID-19 restrictions on research and masking. We will run additional subjects through the end of this grant year and into the next year to make up for time lost due to COVID.

Data Quality Control: We will conduct a detailed data quality-control assessment for all C4 and C5 datasets, building a complete, standardized dataset for eventual delivery to NASA. This process will include identifying more anomalies (not just missing, brief dropout, noise bursts, erroneous values, etc.) in all datasets so that analysis programs can be robust to such data features.

Data Analysis: All findings to date represent the results of interim analyses, given the limited number of control subjects. We are working to finalize analyses of the responses of ROBoT-r performance to HERA countermeasures and submit a manuscript for peer review by the end of this grant year.

NOTE: Extended to 1/31/2020 per K. Ohnesorge/HRP JSC (Ed., 5/24/18)

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) C4 and C5 campaigns. In this project, we will deploy both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus up to 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if possible.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS (near-infrared spectroscopy), EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

In Year 3 of this project, the following tasks have been completed.

ROBoT-r v6.3 Software Deployment: While ROBoT-r v6.2 remained deployed in HERA for Campaign 4, v6.3 was deployed for Campaign 5. This upgrade included an important upgrade that prevents any accidental bumping of the hand controllers between trials from causing a trial abort, as well as a few minor modifications to the feedback displays provided after each trial. These display modifications were made based on discussions with ROBoT-r trainers to ensure consistency of feedback between research and operations use of the ROBoT-r task. In addition, at the start of HERA C5M2, a patch was deployed to speed up the recycling process between ROBoT-r runs to help maintain the task timing and schedule for ROBoT-r performance.

HERA Data Collection: In the past year, we completed data collection for HERA Campaign 4 Mission 5, HERA Campaign 5 Mission 1, and initiated data collection for HERA Campaign 5 Mission 2. In each case, Dr. Ivkovic traveled to Houston to confirm appropriate setup of the system and conducted all crew familiarization (with both ROBoT-r and NINscan-SE), all crew training, and all baseline data collection. ROBoT-r and NINscan-SE data was also validated (to confirm the appropriate data was being collected) prior to hatch-closing for each mission. Data collection included the ROBoT-r behavioral performance data and multi-modal NINscan brain and physiological data.

In addition, following the finalization of the HERA C4M5 crew, we began recruiting control subjects at Massachusetts General Hospital for HERA Campaign 4. To date, we have recruited n=10 control subjects, and completed running n=7, with no off-nominal data collection issues.

HERA Data Analysis: Analyses to date remain preliminary, given the limited number of control subjects. However, a number of features have been clearly identified.

• Weighted scores increase steadily and significantly throughout the ~60-day pre-/during-/post-HERA periods, representing improved accuracy at point of contact between Canadarm2 and the HTV-II vehicle. The proportion of successful captures also increases over this period.

• Duration to completing vehicle capture decreases steadily and significantly over this same period. Increased speed combined with the improved performance is a hallmark of learning, which appears to continue throughout the 60 day missions (which represent ~10-12 hours of hands-on ROBoT-r performance).

• Performance is significantly affected by run difficulty, with the highest difficulty resulting in significantly poorer and slower performance.

• There were notable and significant differences in overall performance across crews.

• In preliminary comparisons between HERA subjects and controls, we found controls performed slightly but significantly worse than HERA participants overall. Interestingly, controls performed better but slower in the high difficulty levels, suggesting a somewhat different strategy (slow and careful) compared to HERA subjects (faster but less accurate).

• Physiological data from NINscan demonstrated significant differences between HERA crews and controls in heart rate (HERA>Controls). Both groups exhibited changes in heart rate, as well as frontal pole and dorsolateral prefrontal brain activation within runs, suggesting progressive “activation” as the more challenging end of the run approached.

Given the limited number of controls, the above findings are preliminary and we cannot state any firm conclusions regarding the differences between HERA crewmembers and controls, for either behavioral performance or for physiological variables.

Dissemination: The results to date of ROBoT-r data collection were presented at the Human Research Program Investigator Workshop (HRP IWS) conference in Galveston, TX in late Jan 2019, and portions of this effort were included in the Master’s Thesis of Dr. Stijn Thoolen at Kings College, London.

Remainder of Year 3: In the remaining 2 months of grant year 3 we anticipate completing the following activities:

Data Collection: Data collection and support for C5M2 is underway and will continue through mid-July 2019. We will also continue to actively recruit additional control subjects, and steadily run those through this year and next.

Data Quality Control: We will conduct a detailed data quality-control assessment for all C4 datasets as well as for C5M1. This will include identifying more subtle anomalies (dropout, noise, erroneous values, etc.) in all datasets so that analysis programs can be robust to such data features. C5M2 will undergo the same process at the beginning of the next grant year.

Data Analysis: We will work to complete the interim analysis of our NINscan data during the remainder of this grant year, with analyses designed to address our Specific Aims.

NOTE: Element change to Human Factors & Behavioral Performance; previously Behavioral Health & Performance (Ed., 1/18/17)

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) C4 and C5 campaigns. In this project, we will deploy both systems to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus up to 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if possible.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS, EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be supported, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as various commercial possibilities.

In Year 2 of this project, the following tasks have been completed.

ROBoT-r v6.3 Software: While ROBoT-r v6.2 remains deployed in HERA for Campaign 4, additional modifications have been underway for the software. This included an important upgrade that prevents any accidental bumping of the hand controllers between trials from causing a trial abort, as well as a few minor modifications to the feedback displays provided after each trial. These display modifications were made based on discussions with ROBoT-r trainers to ensure consistency of feedback between research and operations use of the ROBoT-r task.

HERA Data Collection: At the time of the first annual report, HERA Campaign 4 Mission 1 was complete and preparations for C4M2 were underway. C4M2 was completed through mission day (MD) 22, at which point Hurricane Harvey required evacuation of the facility, thus aborting the mission. C4M3 was completed without incident, as was C4M4. Currently, C4M5 is underway. In each case, Dr. Ivkovic traveled to Houston to confirm appropriate setup of the system and conducted all crew familiarization (with both ROBoT-r and NINscan-SE), training, and all baseline data collection. ROBoT-r and NINscan-SE data was also validated (to confirm the appropriate data was being collected) prior to hatch-closing for each mission. Data was collected nominally during each mission. We obtained 97.7% of ROBoT-r data expected from Missions 1-4, and 96.8% of the NINscan physiological data.

HERA Data Analysis: Analyses to date have been limited to quality control and very preliminary assessments. ROBoT-r data is demonstrating learning curves consistent with expectations based on HERA C3 testing. NINscan data is also showing basic phenomena consistent with expectations including inter-hemispheric functional connectivity at rest, brain activation associated with engagement in the ROBoT-r task, and suppression of low-frequency EEG waveforms associated with task engagement. Analysis procedures are being finalized to address our specific aims and an interim analysis will be conducted when all data from Campaign 4 is available.

Controls: We completed running controls for our HERA C3 mission and then swapped hardware and upgraded software at Massachusetts General Hospital (MGH) to match the hardware/software versions in HERA C4. We are now recruiting controls for HERA C4, seeking to match HERA subjects as closely as possible. These subjects will continue to be run through much of year 3 of the project.

Dissemination: The results to date of ROBoT-r data collection were presented at the Human Research Program (HRP) Investigator Workshop (IWS) conference in Galveston, TX in late January 2018.

In the remaining 2 months of grant year 2 we anticipate completing the following activities.

HERA C4M5 Completion: Mission 5 is the replacement for the aborted Mission 2. This mission is scheduled hatch opening on 6/15/2018, followed by a 1-week period of post-mission data collection. At that point we will have completed all of Campaign 4 subjects and will be able to pool data across C4 subjects to characterize their performance over the course of the 45-day missions. Research on this project will continue in Campaign 5, following a planned 6-month delay in startup, and our main research questions will be addressed once we complete data collection for all C4 control subjects.

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory over the next several months, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) 2016 campaign. We propose to deploy both in this project to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if available.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance; (iii) identification of potential predictors of future ROBoT performance; and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.

Regarding NINscan-SE, no current NIRS, EEG, or polysomnography device has both the portability and the multi-use features of the system we will be deploying. This system could thus have substantial novel Earth applications. Hospital monitoring applications could include long-duration, non-invasive brain monitoring in the NeuroICU following stroke or traumatic injury, for which no similar technology exists. Real-time, in-office brain activation assessment could also be enabled, for assessment of psychiatric states, for monitoring the neural effects of cardiovascular or psychoactive drugs or other therapies, or for brain monitoring during rehabilitation. Mobile monitoring could perhaps have an even larger impact outside the hospital setting. A wearable monitor would enable ambulatory syncope monitoring, or multi-parameter ambulatory epilepsy monitoring. If deployed in emergency settings, NINscan-SE could potentially be used to detect cerebral or abdominal hemorrhage, ischemia, and/or cortical spreading depression by first responders. Home monitoring uses include various sleep disorders, as well as any of the various commercial possibilities indicated below.

ROBoT v6.2 Software: A new version of ROBoT was generated and deployed to HERA for Campaign 4. This version of ROBoT added (1) support for the newly-fabricated hand-controllers, (2) a new setup tab and associated action buttons so that the operations and research versions of ROBoT can coexist within the same code-base, (3) a post-session comments box, (4) revised feedback for crewmembers that is in better alignment with NASA operations (10=best score, 0=worst), (5) a custom set of emergency trials specific to our C4 protocol, plus (6) various bits of code cleanup and bug fixes. The tab and action buttons were key to enable seamless transition between the “ops” version of ROBoT (which does not save data and displays different feedback) and ROBoT (which does save data). Support for the new controllers is supplemental, meaning the ROBoT system can now be configured to use either legacy or new-style hand controllers as needed. The post-session comments box allows subjects to type in immediately following a set of 12 runs any issues that were encountered (problems with system setup, interruptions during performance, unexpected software glitches encountered, and so on).

NINscan-SE Hardware: Our NINscan-SE prototype was also reconfigured for use in HERA C4. This involved two hardware changes. The first involved developing a new auxiliary sensor component module. The previous NINscan-SE auxiliary sensors were designed specifically for polysomnography, whereas the new module incorporates sensor leads for 3-channel EEG and 2-channel EOG (to minimize wiring that users need to manage). As with the prior module, it simply needs to plug into the base recorder box for use. In addition, we modified the internal electronics of the recorder box to incorporate a second reference channel. This was done so that our F3/F4 EEG channels could be referenced to the contralateral mastoid for more robust and noise-resistant measurements.

Training Materials: New training materials were also developed for HERA C4. While the ROBoT familiarization video from HERA C3 could still be used, we needed to revise the user instructions to reflect a change in login and setup procedure screens, interpreting the new evaluation screens, what to enter in the post-session survey/comments box, and description of the pre-task resting baseline recording period for assessing the default mode network activity. The NINscan-SE instructions needed to be revised to reflect the new sensor module and electrode positioning scheme relative to its deployment in HERA C3.

HERA C4M1 Data Collection: The new version of the ROBoT software was delivered to HERA in February 2017. Dr. Ivkovic traveled to Houston to confirm appropriate setup of the system and conducted all Mission 1 crew familiarization (with both ROBoT and NINscan-SE), training, and all baseline data collection. ROBoT and NINscan-SE data was also validated (to confirm the appropriate data was being collected) prior to hatch-closing, which occurred on 5/6/2017.

In the remaining 2 months of the grant year we anticipate completing the following activities:

HERA C4M1 Completion: Mission 1 is ongoing and scheduled for hatch opening on 6/19/2017, followed by a 1-week period of post-mission data collection. Thus, we expect to complete Mission 1 (n=4) before the end of June. Upon completion of this phase, we will collect all ROBoT data and NINscan-SE data and begin the quality control and the initial data analysis phase.

HERA C4 M2: The HERA Mission 2 crew (n=4) is scheduled to begin training on 7/20/2017 with hatch closing on 8/5/2017. Dr. Ivkovic will again travel to Houston for the training-to-hatch-closing phase of M2, completing the same tasks as for Mission 1. The remainder of M2 will be completed during year 2 of this project.

Controls: We are currently running controls for our HERA C3 mission. Immediately following those controls we will begin running controls for HERA C4. These subjects will be performing ROBoT sessions on the same schedule as the individuals in HERA C4, including the same NINscan-SE recording protocols. These subjects will continue to be run through most of year 2 of the project.

Currently the Robotic On-Board Trainer (ROBoT) is used operationally by astronauts both on the ground and on the International Space Station (ISS) to practice Canada Arm activities. Our group is helping adapt ROBoT for research use and for quantitative performance assessment. In addition, our group is developing and testing NINscan-SE: a multi-use system for measuring brain and physiological function. Both ROBoT and NINscan-SE are being characterized and validated in our laboratory over the next several months, and will undergo analog feasibility testing during the Human Exploration Research Analog (HERA) 2016 campaign. We propose to deploy both in this project to:

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

To achieve these aims, we will recruit up to 32 crewmembers from eight 45-day missions in the HERA facility during Campaigns 4 and 5, plus 32 control subjects. HERA and control participants will all perform ROBoT tasks plus undergo physiological monitoring 2x/week, on matching schedules, thus enabling us to differentiate changes in operational performance due to practice over time from any changes due to HERA sequestration. In addition, two “unexpected operational emergency” events will be introduced in the first and last weeks of each HERA mission. These will consist of an acute need to capture a wayward satellite traveling near the limits of Canada Arm capabilities.

We will also work with the Behavioral Health and Performance (BHP) Element and other HERA investigators to coordinate ROBoT and physiological data collection before, during, and after one or more countermeasure (CM) deployments during the HERA missions. CM(s) may include a lighting intervention, a Virtual Space Station-based behavioral intervention, diet, exercise or some other intervention. The experimental design will depend on the nature of the CM. We will test hypotheses that the CM(s) generate detectable changes in ROBoT performance and rest/task (neuro)physiology recordings. We will also compare ROBoT performance to the standardized Behavioral Core Measures (BCM), if available.

The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance, (iii) identification of potential predictors of future ROBoT performance, and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.