NASA astronauts and ground crew need to maintain high levels of cognitive performance to ensure successful completion of space missions and safety of astronauts. Astronauts and ground crew are exposed to sleep loss arising from the shifting and extended work schedules often associated with their missions. Therefore, astronauts and ground crew are at risk for fatigue-related accidents. Accurate diagnosis of fatigue is a major challenge. Subjective sleepiness is reported significantly less often than observed objective performance decrements, indicating that self-diagnosis is inaccurate. Sleep deprivation reduces activation in the prefrontal cortex (PFC), a brain region important for cognitive performance. A recently-developed technology, through National Space Biomedical Research Institute (NSBRI) support to Dr. Gary Strangman (co-mentor on this project), quantifies hemodynamic changes in oxygenated and deoxygenated blood within specific brain regions using Near-Infrared Spectroscopy (NIRS). Standard methodology for assessing hemodynamic changes requires large, expensive functional magnetic resonance imaging (fMRI) or positron emission tomography (PET) techniques that are impractical for use in space or most work environments. In contrast, ambulatory NIRS monitoring is relatively portable, inexpensive, simple to apply and can record over 24 hours of data in a single session.

We used NIRS technology to examine PFC activity in experimental volunteers participating in inpatient chronic sleep restriction (CSR) and acute sleep deprivation (ASD) protocols. NIRS monitoring during these protocols allowed us to address the specific aims of the project: 1) To test the hypothesis that hemodynamic responses in the PFC to the psychomotor vigilance task (PVT) will exhibit a circadian rhythm. 2) To test the hypothesis that hemodynamic responses in the PFC to the PVT will be reduced during CSR and ASD. 3) To test the hypothesis that hemodynamic fluctuations in the PFC are associated with PVT performance deficits.

In the past two years, we have successfully collected NIRS recordings from over 1000 cognitive performance testing sessions at multiple circadian phases in 9 participants on the CSR protocol and over 150 testing sessions in 13 participants on the ASD protocol. PFC hemodynamic responses throughout each PVT session were quantified using both block averaging and deconvolution techniques. Metrics of the hemodynamic response, including peak amplitude and area under the curve (AUC) were included in mixed-model analyses with circadian phase, length of time awake, and CSR or non-CSR condition as discrete variables. We identified a significant effect of length of time awake and circadian phase on hemodynamic response using the block-averaged method, addressing Specific Aim 1. We did not find a significant effect of CSR on hemodynamic response, addressing Specific Aim 2. Analyses of the effect of ASD on hemodynamic response are pending. To address Specific Aim 3, we assessed the relationship between PFC hemodynamic response and PVT performance using the deconvolution method, since it allows use of all data for each PVT session. We found that PVT sessions with HbO2 peak amplitude or AUC less than baseline median were significantly more likely to contain PVT lapses. When peak amplitude was below baseline median compared to above baseline, the relative risk of PVT lapse was 2.0.

The findings from this study demonstrate the potential use of NIRS technology to objectively monitor PFC decrements associated with reduced performance. NIRS monitoring of PFC may lead to the improved identification and prediction of decreased performance and times of sleepiness in shift-working populations, including astronauts, ground crew, firefighters, pilots, health care providers, truck drivers, and military personnel and therefore reduce fatigue-related accidents.

For Specific Aim 1, NIRS data relative to melatonin phase (a circadian marker) were used to quantify the circadian rhythmicity in the hemodynamic response in the prefrontal cortex (PFC) in response to PVT presentation. We found a significant effect of circadian phase and length of time awake on PFC activation.

For Specific Aim 2, comparisons of hemodynamic responses to PVT from the beginning of the CSR protocol compared to responses at the end of the CSR protocol and between CSR and control participants were used to quantify the impact of CSR on brain activation in the PFC. We did not find a significant effect of CSR on PFC activation.

For Specific Aim 3, the PFC response and PVT lapses were analyzed between baseline and non-baseline days to identify a relationship between PFC activation and PVT performance. When PFC activation was lower than baseline, we found a significantly higher relative risk of PVT lapses in the same session.

NASA astronauts and ground crew need to maintain high levels of physical and cognitive performance to ensure successful completion of space missions and the safety of astronauts. Astronauts and ground crew are exposed to sleep loss arising from shifting and extended work schedules commonly associated with their missions. As a result, many astronauts and ground crew are at risk for fatigue-related accidents that can endanger the success of space missions and personal safety. A major challenge in combating fatigue is accurate diagnosis. Subjective sleepiness is reported significantly less often than observed objective performance decrements, indicating that self-diagnosis is inaccurate. Recent evidence suggests that sleep deprivation reduces activation in the prefrontal cortex (PFC), a brain region known to be important for executive function and cognitive performance. A recently-developed technology, developed substantially by co-mentor Dr. Strangman with NSBRI support, allows for the quantification of hemodynamic changes in oxygenated and deoxygenated blood within the brain using Near-Infrared Spectroscopy (NIRS). NIRS detects regional brain activity alterations associated with these hemodynamic changes. Current methodology for assessing hemodynamic changes requires large, expensive functional magnetic resonance imaging or positron emission tomography techniques that are impractical for use in space or most work environments. In contrast, ambulatory NIRS monitoring is relatively portable, relatively inexpensive, simple to apply and can record over 24 hours of data in a single session. Therefore, this non-invasive method for assessing regional brain activity overcomes the prohibitive restrictions of other neuroimaging systems and has the additional advantages of multi-hour recordings and ambulatory monitoring.

We are using NIRS technology to examine PFC activity in experimental volunteers participating in chronic sleep restriction (CSR) and acute sleep deprivation (ASD) protocols. NIRS monitoring during these protocols will allow us to address our specific aims: 1) To test the hypothesis that hemodynamic responses in the PFC to the psychomotor vigilance task (PVT) will exhibit a circadian rhythm. 2) To test the hypothesis that hemodynamic responses in the PFC to the PVT will be reduced during CSR. 3) To test the hypothesis that hemodynamic fluctuations in the PFC associated with delta wave sleep activity will increase in frequency following a 30-hour ASD.

In the past year, we have developed standard operating procedures to implement NIRS monitoring of the PFC during cognitive performance testing. We have successfully collected NIRS recordings from 400 cognitive performance testing sessions at multiple circadian phases in 4 participants on the CSR protocol, and should complete collection from a 5th participant in October 2013. We also modified our 3rd specific aim to conduct NIRS monitoring of PFC during sleep in volunteers immediately after a 30-hour ASD. We are developing the standard operating procedures to monitor PFC hemodynamic changes during sleep. We are concurrently amending the data analysis methods originally developed by Dr. Strangman to address our specific aims. These data analyses involve block-averaging, power spectral density, and deconvolution methods.

In the upcoming year, we plan to record and analyze NIRS data from an additional 5 participants on the CSR protocol, and 12 participants on the ASD protocol for a total of 22 participants by November, 2014. Results from this study will inform future use of NIRS technology to objectively monitor sleepiness and reduce fatigue-related accidents. Our results may lead to the improved identification and prediction of sleepiness and decreased performance in shift-working populations, including astronauts, ground crew, firefighters, pilots, health care providers, truck drivers, and military personnel.

Specific Aims 1 and 2: Standard operating procedures were developed and tested to use Near-Infrared Spectroscopy (NIRS) during the 32-day chronic sleep restriction (CSR) study. These were required both to collect data cleanly but also to ensure no other data collection (e.g., polysomnography) for the CSR study were negatively affected. We have collected NIRS recordings from over 400 cognitive performance testing sessions (from 5 participants) during an inpatient forced desynchrony (FD) protocol with CSR in which participants complete cognitive tests across all circadian phases. We have modified analysis software developed by Dr. Strangman for use in our experimental conditions. Preliminary assessment of the hemodynamic response to individual psychomotor vigilance task (PVT) trial presentation reveals an immediate decrease in oxygenated blood, followed by a larger increase, while deoxygenated blood shows an inverse response. This pattern of hemodynamic response has been described in the visual cortex in previous studies using visual stimuli and demonstrates the operational success of the data collection thus far. We will continue data collection on 5 additional participants. For specific aim 1, analyses of the NIRS data and relative to melatonin phase (a circadian marker) will quantify the circadian rhythmicity in the hemodynamic response in the prefrontal cortex (PFC) in response to PVT presentation.

For specific aim 2, comparisons of hemodynamic responses to PVT from the beginning of the CSR protocol compared to responses at the end of the CSR protocol and between CSR and control participants will allow us to quantify the impact of CSR on brain activation in the PFC.

Specific Aim 3: We redesigned Aim 3 to investigate the impact of a 30-hour acute sleep deprivation on PFC activity during the following recovery sleep. NSBRI approved this change. We are developing the standard operating procedures necessary to conduct NIRS monitoring during sleep, and plan to implement these procedures in October.

Astronauts and supporting ground crew need to maintain high levels of physical and cognitive performance to ensure successful completion of space missions and safety of the astronauts. Astronauts and ground crews are often exposed to work challenges that are not conducive for restful sleep. Sleep loss can arise from shifting and extended work schedules that are commonly associated with space exploration. As a result, many astronauts are at risk for fatigue-related accidents that can endanger the success of space missions and personal safety. A major challenge in combating fatigue is accurate diagnosis. Subjective reporting of sleepiness is frequently significantly less than that obtained from objective measurements, indicating that self-diagnosis is inaccurate, even without including motivational reasons for an individual to report higher level of alertness than (s)he truly feels.

Preliminary evidence suggests that sleep deprivation reduces activation in the prefrontal cortex, which is known to be important for executive function and cognitive performance. A recently-developed technology, substantially developed with NSBRI support, allows for the quantification of oxygenated and de-oxygenated blood within the brain using near-infrared spectroscopy (NIRS). NIRS detects regional brain activity alterations associated with hemodynamic changes. Previous methodology for assessing hemodynamic levels required large, expensive functional magnetic resonance imaging (MRI) or positron emission tomography (PET) techniques that are impractical for use in space or most work environments. In contrast, NIRS technology is a highly portable and relatively inexpensive, and simple device for assessing regional brain activity.

Here, I propose to use NIRS to measure regional brain activation in the prefrontal cortex during performance testing and during sleep in participants experiencing chronic sleep restriction. I will test the effects of sleep restriction at different circadian phases on prefrontal cortex activation during a cognitive performance task and during deep sleep. Results from this study can lead to the potential use of NIRS technology to objectively monitor sleepiness and reducing fatigue-related accidents.