Effects of Long-Duration Spaceflight on General and Spatial Cognition and Its Neural Basis

Official title

Temporal Nature of Cognitive and Visuospatial Brain Domain Changes During Long-Duration Low-Earth Orbit Missions (Spatial Cognition)

Overview

This study investigates the effects of extended-duration spaceflight (12-month International Space Station missions) 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.

Detailed description

This is an international proposal consisting of two projects with synergistic aims that will be carried out in a joint effort by the National Aeronautics and Space Administration (NASA) and the German Aerospace Center (DLR) as well as the European Space Agency (ESA). The project targets NASA's particular interest in studying the 'Cognitive-perceptual-visuospatial brain domain changes due to isolation and confinement' as part of the Complement of Integrated Protocols for Human Exploration Research (CIPHER) project on the International Space Station (ISS). The collected data will 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 ISS missions. Using state-of-the-art neuroimaging techniques, investigators will determine the biological basis for any changes in cognitive performance, with a focus on hippocampal plasticity and spatial cognition. 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, investigators 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 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.

Interventions

• Other Spaceflight
  Exposure to the spaceflight environment on the International Space Station for 2, 6, or 12 months.
• Other Controls
  No intervention

Primary outcome measures

• Cognitive performance [Time frame: Change from pre-flight performance (average of tests performed 180, 120 and 60 days prior to launch) to in-flight performance (average of all tests: 1 month mission = 1 test, 2 months = 2 tests, 6 months = 6 tests, 12 months = 12 tests)]
• Local task activation Cognition [Time frame: Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight local task activation (investigated 5 days and 30 days after return to Earth)]
• Spatial cognition performance [Time frame: Change from pre-flight performance (average of tests performed 180, 120 and 60 days prior to launch) to in-flight performance (average of all tests: 1 month mission = 1 test, 2 months = 2 tests, 6 months = 4 tests, 12 months = 7 tests)]
• Structural brain changes [Time frame: Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight (investigated 5 days and 30 days after return to Earth)]
• Local task activation Spatial Cognition [Time frame: Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight local task activation (investigated 5 days and 30 days after return to Earth)]
• Brain-Derived Neurotropic Factor (BDNF) [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]

Secondary outcome measures (7)

• Insulin-like Growth Factor 1 (IGF-1) [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]
• Vascular Endothelial Growth Factor (VEGF) [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]
• Oxytocin [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]
• Interleukin (IL)-1 [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]
• Interleukin (IL)-1ra [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]
• Interleukin (IL)-10 [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]
• Tumor Necrosis Factor a (TNFa) [Time frame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)]

Eligibility criteria

Inclusion criteria

• Astronauts (according to NASA requirements)
• Normal, healthy volunteers (astronaut surrogates) - Astronaut surrogates will be matched for sex, age and education relative to astronauts

Exclusion criteria

For astronauts and normal, healthy volunteers (astronaut surrogates):

• Subjects that do not comply with the MRI testing requirements. The following and other conditions may exclude the subject from MRI scanning or require additional examination to assess specific contraindications:

• Tinnitus;
• Sensori-neural hearing loss > 30 decibels (dB);
• Pace-maker or internal defibrillator;
• metallic implants (e.g. orthopedic plates after bone fractures, joint replacements, surgical staples or clips, artificial heart valves, stents, cava filters);
• Metallic splinters (e.g. after an accident or due to war injury);
• Non-removable dental brace;
• Intrauterine contraceptive devices (IUD) that are not MRI-compatible;
• Cochlear implant (implanted hearing device);
• Medication pump;
• Acupuncture needle;
• Other foreign bodies/objects which are non-removable;
• Pregnancy (or its possibility);
• Previous brain and/or heart surgery.
• Tattoos and/or permanent make-up in the body (some inks contain metallic particles).
• Female subjects in this study are either astronauts or will model those in the astronaut population for whom participation in space missions is not allowed during pregnancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 2 centers

• University of Pennsylvania Perelman School of Medicine — Philadelphia
• Johnson Space Center (JSC) — Houston

Germany · 1 center

• Charité - Universitätsmedizin Berlin — Berlin

Publications

• Basner M, Moore TM, Hermosillo E, Nasrini J, Dinges DF, Gur RC, Johannes B. Cognition Test Battery Performance Is Associated with Simulated 6df Spacecraft Docking Performance. Aerosp Med Hum Perform. 2020 Nov 1;91(11):861-867. doi: 10.3357/AMHP.5602.2020. PMID 33334406
• Afshinnekoo E, Scott RT, MacKay MJ, Pariset E, Cekanaviciute E, Barker R, Gilroy S, Hassane D, Smith SM, Zwart SR, Nelman-Gonzalez M, Crucian BE, Ponomarev SA, Orlov OI, Shiba D, Muratani M, Yamamoto M, Richards SE, Vaishampayan PA, Meydan C, Foox J, Myrrhe J, Istasse E, Singh N, Venkateswaran K, Keune JA, Ray HE, Basner M, Miller J, Vitaterna MH, Taylor DM, Wallace D, Rubins K, Bailey SM, Grabham PMID 33242416
• Basner M, Hermosillo E, Nasrini J, Saxena S, Dinges DF, Moore TM, Gur RC. Cognition test battery: Adjusting for practice and stimulus set effects for varying administration intervals in high performing individuals. J Clin Exp Neuropsychol. 2020 Jul;42(5):516-529. doi: 10.1080/13803395.2020.1773765. Epub 2020 Jun 15. PMID 32539487
• Nasrini J, Hermosillo E, Dinges DF, Moore TM, Gur RC, Basner M. Cognitive Performance During Confinement and Sleep Restriction in NASA's Human Exploration Research Analog (HERA). Front Physiol. 2020 Apr 28;11:394. doi: 10.3389/fphys.2020.00394. eCollection 2020. PMID 32411017
• Lee G, Moore TM, Basner M, Nasrini J, Roalf DR, Ruparel K, Port AM, Dinges DF, Gur RC. Age, Sex, and Repeated Measures Effects on NASA's "Cognition" Test Battery in STEM Educated Adults. Aerosp Med Hum Perform. 2020 Jan 1;91(1):18-25. doi: 10.3357/AMHP.5485.2020. PMID 31852569
• Scully RR, Basner M, Nasrini J, Lam CW, Hermosillo E, Gur RC, Moore T, Alexander DJ, Satish U, Ryder VE. Effects of acute exposures to carbon dioxide on decision making and cognition in astronaut-like subjects. NPJ Microgravity. 2019 Jun 19;5:17. doi: 10.1038/s41526-019-0071-6. eCollection 2019. PMID 31240239
• Garrett-Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, McKenna MJ, Meydan C, Mishra T, Nasrini J, Piening BD, Rizzardi LF, Sharma K, Siamwala JH, Taylor L, Vitaterna MH, Afkarian M, Afshinnekoo E, Ahadi S, Ambati A, Arya M, Bezdan D, Callahan CM, Chen S, Choi AMK, Chlipala GE, Contrepois K, Covington M, Crucian BE, De Vivo I, Dinges DF, Ebert DJ, Feinberg JI, Gandara JA, George KA, Gou PMID 30975860
• Basner M, Nasrini J, Hermosillo E, McGuire S, Dinges DF, Moore TM, Gur RC, Rittweger J, Mulder E, Wittkowski M, Donoviel D, Stevens B, Bershad EM; SPACECOT Investigator Group. Effects of -12 degrees head-down tilt with and without elevated levels of CO2 on cognitive performance: the SPACECOT study. J Appl Physiol (1985). 2018 Mar 1;124(3):750-760. doi: 10.1152/japplphysiol.00855.2017. Epub 2017 De PMID 29357516

Identifiers

NCT: NCT04856410 · 843851 · 80NSSC19K1046 · 50WB2115

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗