Department of Psychiatry

Penn Behavioral Health

Current Projects

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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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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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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Neurostructural, Cognitive, and Physiologic Changes during a 1-Year Antarctic Winter-Over Mission

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

This proposal primarily addresses the BMed3 Gap on the nature and duration of cognitive performance changes in-flight andpost mission, by assessing neurostructural, cognitive, behavioral, physiologic, and psychosocial changes in maximally N=24-28 crewmembers during a 10-12 month Antarctic winter-over in Concordia station, and in the same number of controls matched to crewmembers based on age, gender, and educational attainment. State-of -the-art quantitative structural and functional magnetic resonance imaging (both resting-state and activated), diffusion tensor imaging, and arterial spin labeled fMRI will be performed in crewmembers and controls 4 months before, immediately after, and 6 months after the mission. During the mission, crewmembers will wear a wrist-watch like device that measures movement activity and proximity to other devices 24/7 to investigate sleep/wake behavior and crew cohesion. Once monthly, subjects will perform the Cognition test battery to quantify changes in cognitive performance. Cognition was specifically designed for high-aptitude astronauts and astronaut surrogates. It consists of 10 brief,validated neuropsychological tests that cover a wide range of cognitive domains. A 24-hour, two-electrode ECG will be performed monthly to investigate systematic changes in heart rate, heart rate variability, objectively assessed workload and sleep fragmentation with time-in-mission. Behavioral alertness will be assessed with a 3 min. Psychomotor Vigilance Test (PVT) on a weekly basis along with brief surveys to assess subjective ratings of mood, workload, stress, sleep quality, tiredness, sickness, and conflicts among crewmembers. The results will be compared with findings from Mars520 and ISS, as many of the variables to be gathered overlap with those successfully obtained by our team in these and other space analog environments. After this project we will have a much better understanding whether, to what extent, and for how long neurostructural and neurofunctional changes are induced in subjects overwintering in the isolated and confined space analog environment of Concordia station.

Supplements to this project have collected data from crewmembers at Neumayer-III, SANAE and Halley Antarctic stations.

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Biomarkers as Predictors of Resiliency and Susceptibility to Stress in Space Flight

Sponsor: NASA; Principal Investigator:  Namni Goel, PhD

This proposal is responsive to the NASA Behavioral Health and Performance gap (BMed5) to find individual characteristics that predict successful adaptation and performance in an isolated, confined and extreme environment, especially for long duration missions. The project also relates to HRP Sleep Gap 4 to identify indicators of individual susceptibilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions. The proposal is also responsive to BMed 1 and BMed 2, and Sleep Gap 2 and Sleep Gap 9. To address these gaps,this proposal will assess biomarkers as predictors of resiliency and susceptibility (individual differences) to performance stress and sleep loss using the HRP Human Exploration Research Analog (HERA) and the IBMP-NASA SIRIUS 18/19 4-month mission at the NEK facility in Russia. We will conduct a ground-based experiment—strongly anchored in our previous laboratory-based research—on N=32 healthy men and women (ages 26-55) in the HERA facility (short-duration analog) and on N=6 healthy men and women (ages 30-55) in the NEK facility (long-duration analog) to determine the predictive validity of a set of relevant, valid and reliable biomarkers for distinguishing those who are more resilient versus those who are more susceptible to the adverse neurobehavioral effects of the combination of high performance demands and total sleep deprivation (TSD) stressors—two conditions commonly experienced in space flight. These biomarkers include the following: cardiovascular measures (blood pressure, heart rate and heart rate variability, stroke volume and cardiac output), salivary cortisol, catecholamines (dopamine, noradrenaline,and adrenaline), an inflammatory marker (C Reactive Protein; CRP), metabolomic markers (via unbiased metabolomics) and microRNAs (epigenetic markers). The project deliverable will be a countermeasure (set of diverse biomarkers) for distinguishing those who are more resilient versus those who are more susceptible to the adverse neurobehavioral effects of high performance demands and sleep loss stressors. If valid markers of such susceptibility can be found, it will be possible to optimize and individualize crew resources, and mitigate stress and other behavioral health and performance risks autonomously during long-duration space flight.

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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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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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Links:

SIRIUS 18/19 4-month mission: http://www.marssociety.org/scenario-of-the-sirius-18-19-4-month-mission/

 


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