Current Projects

ATRD15 National Sleep Study

Sponsor: FAA; Principal Investigator: Mathias Basner, MD, PhD, MSc

The overarching goal of the project is to obtain nationally representative data on the relationship between aircraft noise exposure and residential sleep disturbance. Subjects will be recruited from multiple US airports to participate in a 5-night measurement campaign where physiological (heart rate, body movements) and acoustical data are collected simultaneously. These data will be used to derive current exposure-response functions describing the relationship between the maximum sound pressure level of aircraft noise events and the probability to wake up.

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NSCOR for Evaluating Risk Factors and Biomarkers for Adaptation and Resilience to Spaceflight: Emotional Valence and Social Processes in ICC/ICE Environments

Sponsor: NASA; Principal Investigator: David F. Dinges, PhD

NASA’s vision for successful long-duration exploration missions (LDEM) depends on optimizing human performance, adaptability,and resiliency to reduce individual and crew behavioral risks. To date, the major emphasis in optimizing astronauts for their tolerance to prolonged spaceflight has involved human health and performance countermeasures as well as technologies and tools to ensure safety during exploration. However, considerable evidence suggests that there are individual differences among astronauts in their vulnerabilities to the various stressors of spaceflight. The goal of the proposed NSCOR is to obtain novel information that will help identify individuals who are resilient to the stressors of prolonged human spaceflight, thereby ensuring successful completion ofexploration missions and the preservation of astronaut health over the life of the astronaut. This NSCOR project leverages the NIMH Research Domain Criteria (RDoC) heuristic framework to conduct experimental studies to identify biological domains (molecular,circuitry, physiology) and behavioral domains that relate to individual adaptation and resiliency (as well as behavioral vulnerability) in spaceflight-relevant confined and extreme environments (ICC and ICE). The NSCOR focuses specifically on differences among astronauts in their tolerance of and adaptability to simulated conditions of prolonged spaceflight that impact behavioral health and performance. The NSCOR will provide novel information on the extent to which behavioral and biological factors can be identified that predict astronauts who can maintain positive mood, proactive social processes, a high level of performance and personal wellbeing,while coping with confinement, meaningless work, limited social support, and living in the extreme environmental conditions of space. By utilizing the RDoC framework, three different human confinement analogs and an animal model, the NSCOR will generate data converging on biomarkers of neurobehavioral and neurobiological resilience to the spaceflight conditions. Such a discovery will help in selecting astronauts most likely to maintain human health and performance during long-duration exploration missions.

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Evaluation of SmartSleep Technology for Improving the Efficiency and Restorative Quality of Sleep in Healthy Adults in Order to Mitigate Cognitive Performance Deficits Due to Sleep Restriction and Emergency Awakenings

Sponsor: NASA/TRISH; Principal Investigator: David F. Dinges, PhD

Astronauts must maintain a high level of cognitive performance capability in spaceflight, which depends on their acquiring adequate daily sleep quantity and sleep quality while in space, and on their ability to respond quickly and effectively to emergency events that can occur when they are asleep. Extensive studies have found that sleep in spaceflight is often reduced in duration and of reduced quality, which Earth-based studies show can reduce waking cognitive performance. Sleep medications have been used in spaceflight to promote better sleep quality and longer sleep duration sleep, but these have also been shown to markedly compromise the cognitive performance capability of astronauts when an emergency awakening requires them to function effectively. Thus there is a need for a technology that can improve sleep quality in space and biologically maximize the performance benefits of limited sleep duration, without unduly affecting the ability of astronauts to awaken abruptly due to an inflight emergency. Studies have found that unconscious sound enhancement of EEG slow waves during sleep can increase subsequent cognitive performance. This approach to improving sleep quality and the cognitive benefits of sleep is now available as "SmartSleep," a new technology that enhances slow waves using inaudible acoustic stimulation during sleep. SmartSleep consists of a headband worn during sleep and a sleep app. We propose to evaluate this technology in a controlled, double-blind, laboratory study of non-invasive brain stimulation in healthy normal astronaut-like adults, to evaluate whether slow wave sleep enhancement via the SmartSleep stimulus algorithms could benefit cognitive performance during sleep restriction, and/or decrease the severity and duration of sleep inertia after abrupt awakening from sleep.

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Standardized Behavioral Measures for Detecting Behavioral Health Risks during Exploration Missions

Sponsor: NASA; Principal Investigator: David F. Dinges, PhD

The behavioral health of the crew during a mission to Mars could be challenged due to conditions required by the flight. However there is no standardized method to detect and quantify the magnitude of the risk or its likelihood. The overarching goal of this project is to build on a successful record of unobtrusive, software-based measurement of behavioral health indicators (e.g., mood, cognitive function, physical and mental fatigue, sleep quality) to develop an integrated standardized suite of behavioral health measurement tools that would be quite feasible to implement within the constraints of spaceflight research, ground-based analogs (both short- and long-duration), and prolonged missions in isolate, confined, extreme environments lasting up to 12 months or longer. Achievement of this goal would permit a more rapid and reliable assessment and quantification of the Risk of Adverse Behavioral Conditions Psychiatric Outcomes for exploration class missions. The suite of behavioral medicine measures we are developing will be integrated on Apple's iPad platform for their standardized use in ground analogs relevant to the spaceflight context (i.e., Standardized Behavioral Measures Tool or SBMT. It will include (a) the Cognition battery, (b) Visual Analog Scales (VAS) of perceived mental and physical exhaustion, fatigue, stress, workload, conflict and sleep quality, ( c) actigraphy for monitoring sleep/wake activity, (d) an audio journal, ( e) the Space Dock task as an operational performance measure, and (f) additional non-invasive measures relevant to behavioral medicine informed by a comprehensive literature review. The SBMT will be evaluated for its including the task of taking the information on measurement feasibility, flexibility, and acceptability during post-mission assessments in the participants studied in HERA, Neumayer-III Antarctic station, and ISS. It will be improved as needed, and an operational procedures document will be developed to to make its use convenient and unobtrusive for detecting the incident rate of behavioral health risks in space and on Earth.

The SBMT has been given the operational name Behavioral Core Measures (BCM) by JSC.

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iCOMPARE - CCC

Sponsor: NIH/NHLBI; Principal Investigator:  David Asch, MD; Co-Investigator: David F. Dinges, PhD

In the US and other countries, policy limiting duty hours in graduate medical education has undergone significant revision in the last decade and become a central point of debate. Evidence from human chronobiology and sleep argues for shorter shifts because fatigue leads to errors. However, evidence from operations research argues for more continuity because patient handoffs also lead to errors and may reduce the effectiveness of education necessary to produce independent clinicians. The evidence from both fields is compelling, resulting in uncertainty regarding how to best configure duty hour standards for fatigue management, high quality patient care, and trainee education. In 2011, the Accreditation Council for GraduateMedical Education (ACGME) imposed more restrictive duty hour standards for all trainees. The new duty hours added that post-graduate year 1 (PGY1) trainees (interns) work no more than 16h duty periods in a day. This change greatly increased the frequency of patient handoffs. As a result, alternative work schedules have been proposed that combine longer shifts to maintain continuity of patient care with efforts to manage fatigue.

We propose a cluster randomized trial of 58 Internal Medicine (IM) training programs to compare the current duty hour standards (“Curr” throughout this proposal) with a more flexible schedule (“Flex”) that is grounded in contemporary understanding of sleep and patient safety and defined by three rules: [1] work no more than 80 hours per week; [2] call no more frequent than every 3rd night; [3] 1 day off in 7—all averaged over 4 weeks.

Our primary hypothesis addresses patient safety: 30-day patient mortality under Flex will not exceed (will not be inferior to) mortality under Curr. Our secondary hypotheses address education and sleep and fatigue: (a) Interns in Flex will spend greater time in direct patient care and education compared to interns in Curr; (b) Average daily sleep obtained by interns in Flex will not be less than (will not be inferior to) that of interns in Curr.

iCOMPARE (Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education) will provide the rigorous comparative effectiveness data essential to setting duty hourpolicies that optimize quality of care and the competency of our future physicians. Moreover, the same two schedules, Curr vs. the novel Flex scheme, are being compared in the ongoing FIRST trial in residents in general surgery. The combination of well-designed separate trials in both primarily procedural and nonprocedural fields will fill the unmet need for a high-quality, generalizable body of evidence to inform national duty hour policy.

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Temporal Nature of Cognitive and Visuospatial Brain Domain Changes during Long-Duration Low-Earth Orbit Missions

Sponsors: NASA and DLR/ESA; Co-Principal Investigators: Mathias Basner, MD, PhD; Alexander Stahn, PhD

This is an international collaboration consisting of 2 projects with synergistic aims that will be carried out in a joint effort by DLR/ESA and NASA. It addresses the HRP Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders, HRP's requirement to demonstrate the presence or absence of unacceptable deleterious neurocognitive effects beyond the experience base of six-month expeditions, and to permit extrapolation to early interplanetary expeditions. It also addresses several other critical HRP risks and gaps (e.g., BMed1, BMed2, BMed3, BMed5, CNS-1, SM26). More specifically, we will target NASA's particular interest in studying the 'Cognitive-perceptual-visuospatial brain domain changes due to isolation and confinement' as part of the integrated One-Year Mission Project (i1YMP) on the International Space Station (ISS). The data we propose to collect will - for the first time - reliably demonstrate whether prolonging mission duration to one year will have detrimental effects on general cognitive performance (measured with the Cognition test battery), spatial cognition, structural and functional brain changes in general, and hippocampal plasticity more specifically relative to the shorter 6-month and 2-month missions. Using state-of-the-art neuroimaging techniques (that include fMRI while performing the Cognition test battery in the scanner), we will determine the biological basis for any changes in cognitive performance, with a focus on hippocampal plasticity. Similar data already gathered on the ISS and in several short- and long-duration space analog environments will be used to generate a normative data base for long-duration missions. Finally, we will derive dose-response relationships between cognitive-visuospatial brain domain changes and mission duration that will allow predicting vulnerability to adverse cognitive or behavioral impairment and psychiatric disorders on interplanetary expeditions such as a mission to Mars. The two 7-yr projects will deliver a highly unique and comprehensive set of integrated neuroimaging and neurocognitive tools for the evaluation and ultimately prevention of adverse effects on brain structure and function that lead to behavioral effects associated with exploration-type missions.

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Hybrid Training – A Sensory Stimulation Countermeasure for Long Duration Space Exploration Missions

Sponsor: NASA; Principal Investigator: Mathias Basner, MD, PhD, MSc; Co-Investigator: Alexander Stahn, PhD

This proposal addresses the risk of Adverse Behavioral Conditions and Psychiatric Disorders, and the need to identify and validate countermeasures and effective methods for modifying the habitat/vehicle environment that promote individual behavioral health and performance during exploration class missions (BMed1, BMed7). We propose to investigate the efficacy of physical exercise (using a cycle ergometer) combined with an interactive virtual environment, i.e. Hybrid Training, as a countermeasure for augmenting sensory stimulation during long-duration space missions. This countermeasure will combine validated tools and VR technologiesin a new way to reveal the full potential of Hybrid Training, and take into account (a) key needs that fulfill sensory stimulation, (b)“hedonic adaptation”, i.e. a reduced affective response to stimuli with continued or repeated exposure, (c) delivery schedule, and (d)size, mass and volume requirements. We plan to investigate a crew of N=9 during two 12-14 month Antarctic winter-over missions in Neumayer station (total N=18). We will investigate both immediate and long-term benefits of Hybrid Training. Our primary outcomes are neurostructural and neurofunctional changes assessed with fMRI, and cognitive performance assessed with the Cognition test battery and a virtual maze. We will also assess biochemical markers of stress and neuroplasticity, objective measures of sleep-wake rhythmicity and sleep structure, subjective symptom reports, and group cohesion with unobtrusive proximity measurements as additional outcomes that will provide insights into mechanisms and consequences of the observed structural and functional brain changes, and their reversibility by Hybrid Training. These data will be compared to historic controls from Neumayer station and other Antarctic stations (Concordia, Halley), space analog environments (e.g., Mars500) and the ISS. At the end of the project, we will have a much clearer understanding whether and to what extent the detrimental effects of ICE environments on neuroplasticity and behavioral health can be mitigated by Hybrid Training.

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Hyper.Campus – Effects of Artificial Gravity on Structural and Functional Plasticity During Head-Down Tilt Bed Rest

Sponsor: NASA; Principal Investigator: Alexander C. Stahn, Ph.D.

The overarching aim of this study is to investigate the effects of 60 days of head down tilt bed rest (HDBR) with and without artificial gravity as a countermeasure on structural and functional brain plasticity and their behavioral significance. The experiment will comprise the following specific aims:

  • Investigate the effects of HDBR with and without artificial gravity on gray and white matter volume, subcortical volume, myelination, functional connectivity and task related brain activation.
  • Investigate the effects of HDBR with and without artificial gravity on cognitive performance
  • Investigate the effects of HDBR with and without artificial gravity on biochemical markers of stress and neuroplasticity

All experimental procedures will be conducted on N=24 enrolled subjects in an ongoing 60-day HDBR study sponsored by the European Space Agency (ESA) at the DLR: envihab facility. This 2-year project (approx. 1 to 1.5 years data collection; remainder for analysis) will deliver a comprehensive set of neuroimaging, neurocognitive and physiological assessment tools for the evaluation and ultimately prevention of adverse neurostructural and neurobehavioral effects associated with spaceflight.

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Neural mechanisms underlying the antidepressant effects of sleep deprivation

Sponsor: NIH; Co-Principal Investigators: Philip Gehrman PhD; Hengyi Rao, PhD; Co-Investigator: David F. Dinges, PhD

Despite decades of development of antidepressant treatments, even the most effective interventions often take weeks to achieve symptom relief, and are only effective in a subset of patients who try them. From 40 to 60%of patients with depression experience a rapid and significant improvement of mood with one night of total or partial sleep deprivation (SD). Although the antidepressant effect of SD has been known for decades, the neural mechanisms underlying this effect have not been elucidated. Recent advances in functional neuroimaging have provided new opportunities to investigate state changes in regional brain function, along with a better understanding of the neural networks affected by depression and SD. Previous depression studies from our group as well as others have consistently demonstrated dysfunction in brain networks underlying arousal, emotion regulation, and self-referential processing. Our neuroimaging data in healthy controls shows that SD can change the function of these same networks and these changes are opposite to that seen in depressed patients versus controls. Here we propose to study a group of N=48 antidepressant-free male and female patients with current depression symptom and N=12 healthy controls with no history ofmood disorders before and after SD to provide mechanistic insight into the neural substrates underlying the antidepressant effects of SD. We hypothesize that SD-induced concurrent functional activity and connectivity changes in multiple brain networks related to different depressive symptom dimensions including emotion regulation, attention, arousal, self-referential, and reward processing will underlie the rapid and transient antidepressant effects of SD. Using an ABA design, multimodal brain imaging along with more traditional electroencephalographic (EEG) and neurobehavioral testing data will be acquired at baseline after normal sleep, during one night of total SD, and after one night of recovery sleep using a 5-day in laboratory protocol during which subjects will be continuously monitored by trained staff. An interdisciplinary team of researchers with expertise in depression, neuroimaging, sleep, and chronobiology will collaborate to carry out this project using state-of-the-art approaches. Results from this project will not only elucidate neural mechanisms underlying the rapid antidepressant effects of SD, but also yield brain-based biomarkers to predict or monitor individual responses to SD and potentially novel targets for pharmacological and neuromodulatory interventions.

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Advanced Algorithms for the Prediction of Adverse Cognitive and Behavioral Conditions in Space

Sponsor: NASA/TRISH; Principal Investigator: Mathias Basner, MD, PhD, MSc

This study utilizes Reaction Self-Test (RST) data collected by the PI and his team in N=24 astronauts on 6-month ISS missions, arguably the largest cognitive data set ever collected in spaceflight. RST consists of a survey module and a3-minute version of the Psychomotor Vigilance Test (PVT). Our main objective is to additionally obtain data on key environmental stressors (i.e., CO2 levels, temperature, noise, and radiation) and combine them with RST data and other operational data collected by the PI and his team. All data will be integrated in one carefully annotated database, which will be delivered to NASA at the end of the project and could be later amended and mined by other researchers. We will then develop an individualized dynamic prediction model that informs future PVT performance based on environmental data, survey data, prior PVT administrations, and person-specific characteristics using state-of-the-art machine learning techniques such as functional concurrent regressions and neural networks for time series forecasting. We will perform model selection and identify those variables that have the highest predictive value for PVT performance and could preferentially be collected on future spaceflight missions to inform relevant changes in cognition and behavioral health. At the end of the study, we will deliver an algorithm to NASA that, for the first time, can predict adverse cognitive conditions in astronauts early and with an unprecedented precision (Deliverable 3). The predictive algorithms can be translated to several settings on Earth where high performing individuals have to sustain high levels of cognitive performance while facing several environmental or other challenges (e.g., US Navy personnel on submarines).

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If you are interested in participating in an “Anonymous Survey on Confinement during the COVID-19 Pandemic” (Dinges et al. UEP Survey 2020), please click the link below for additional information:

https://clinicalresearch.itmat.upenn.edu/clinicaltrial/6429/covid19-covid-19-confinement-survey/

 


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