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

NCT04856410 | Enrolling By Invitation

• 3 other identifiers: 84385180NSSC19K104650WB2115
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Brain Structure; Cognitive Performance

Keywords

Astronauts; Spaceflight; Cognition; Long Duration Spaceflight

Outcome Measures

Primary Outcomes (6)

• Cognitive performance

  Cognitive efficiency across domains as determined with the Cognition test battery

  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

  fMRI local task activation while performing the MRI version of Cognition in the scanner

  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

  Accuracy and reaction times for each cognitive task as determined with the Spatial Cognition test batteries

  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

  Structural brain changes assessed with MRI

  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

  fMRI local task activation while performing visuospatial tasks in the scanner

  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)

  Changes in Brain-Derived Neurotropic Factor (BDNF)

  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 Outcomes (7)

• Insulin-like Growth Factor 1 (IGF-1)

  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)

  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

  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

  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

  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)

Study Arms (3)

6-Month Arm

EXPERIMENTAL

Astronauts on 6-month International Space Station missions will be exposed to spaceflight for a duration of 6 months. Biometric and cognitive data will routinely be collected.

Other: Spaceflight

12-Month Arm

EXPERIMENTAL

Astronauts on 12-month International Space Station missions will be exposed to spaceflight for a duration of 12 months. Biometric and cognitive data will routinely be collected.

Other: Spaceflight

No Intervention

EXPERIMENTAL

Subjects matched to 12-month astronauts that stay on Earth and are investigated at similar time points.

Other: Controls

Interventions

Spaceflight OTHER

Exposure to the spaceflight environment on the International Space Station for 2, 6, or 12 months.

12-Month Arm; 6-Month Arm

Controls OTHER

No intervention

No Intervention

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Aeronautics and Space Administration (NASA): collaborator
• DLR German Aerospace Center: collaborator
• Charite University, Berlin, Germany: collaborator

Study Sites (3)

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Johnson Space Center (JSC)

Houston, Texas, 77058, United States

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Related Publications (21)

• 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 BACKGROUND

• 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 P, Costes SV, Mason CE, Beheshti A. Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration. Cell. 2020 Nov 25;183(5):1162-1184. doi: 10.1016/j.cell.2020.10.050.

  PMID: 33242416 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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, Goutsias J, Grills GS, Hargens AR, Heer M, Hillary RP, Hoofnagle AN, Hook VYH, Jenkinson G, Jiang P, Keshavarzian A, Laurie SS, Lee-McMullen B, Lumpkins SB, MacKay M, Maienschein-Cline MG, Melnick AM, Moore TM, Nakahira K, Patel HH, Pietrzyk R, Rao V, Saito R, Salins DN, Schilling JM, Sears DD, Sheridan CK, Stenger MB, Tryggvadottir R, Urban AE, Vaisar T, Van Espen B, Zhang J, Ziegler MG, Zwart SR, Charles JB, Kundrot CE, Scott GBI, Bailey SM, Basner M, Feinberg AP, Lee SMC, Mason CE, Mignot E, Rana BK, Smith SM, Snyder MP, Turek FW. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight. Science. 2019 Apr 12;364(6436):eaau8650. doi: 10.1126/science.aau8650.

  PMID: 30975860 BACKGROUND

• 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 Dec 14.

  PMID: 29357516 BACKGROUND

• Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for Spaceflight in a Sample of Highly Educated Adults. Aerosp Med Hum Perform. 2017 Oct 1;88(10):937-946. doi: 10.3357/AMHP.4801.2017.

  PMID: 28923143 BACKGROUND

• Basner M, Savitt A, Moore TM, Port AM, McGuire S, Ecker AJ, Nasrini J, Mollicone DJ, Mott CM, McCann T, Dinges DF, Gur RC. Development and Validation of the Cognition Test Battery for Spaceflight. Aerosp Med Hum Perform. 2015 Nov;86(11):942-52. doi: 10.3357/AMHP.4343.2015.

  PMID: 26564759 BACKGROUND

• Basner M, Dinges DF, Mollicone DJ, Savelev I, Ecker AJ, Di Antonio A, Jones CW, Hyder EC, Kan K, Morukov BV, Sutton JP. Psychological and behavioral changes during confinement in a 520-day simulated interplanetary mission to mars. PLoS One. 2014 Mar 27;9(3):e93298. doi: 10.1371/journal.pone.0093298. eCollection 2014.

  PMID: 24675720 BACKGROUND

• Basner M, Dinges DF, Mollicone D, Ecker A, Jones CW, Hyder EC, Di Antonio A, Savelev I, Kan K, Goel N, Morukov BV, Sutton JP. Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2635-40. doi: 10.1073/pnas.1212646110. Epub 2013 Jan 7.

  PMID: 23297197 BACKGROUND

• Mendt S, Gunga HC, Felsenberg D, Belavy DL, Steinach M, Stahn AC. Regular exercise counteracts circadian shifts in core body temperature during long-duration bed rest. NPJ Microgravity. 2021 Jan 5;7(1):1. doi: 10.1038/s41526-020-00129-1.

  PMID: 33402671 BACKGROUND

• Chouker A, Stahn AC. COVID-19-The largest isolation study in history: the value of shared learnings from spaceflight analogs. NPJ Microgravity. 2020 Oct 22;6:32. doi: 10.1038/s41526-020-00122-8. eCollection 2020.

  PMID: 33110938 BACKGROUND

• Friedl-Werner A, Brauns K, Gunga HC, Kuhn S, Stahn AC. Exercise-induced changes in brain activity during memory encoding and retrieval after long-term bed rest. Neuroimage. 2020 Dec;223:117359. doi: 10.1016/j.neuroimage.2020.117359. Epub 2020 Sep 10.

  PMID: 32919056 BACKGROUND

• Roberts DR, Stahn AC, Seidler RD, Wuyts FL. Towards understanding the effects of spaceflight on the brain. Lancet Neurol. 2020 Oct;19(10):808. doi: 10.1016/S1474-4422(20)30304-5. Epub 2020 Sep 16. No abstract available.

  PMID: 32949538 BACKGROUND

• Maggioni MA, Merati G, Castiglioni P, Mendt S, Gunga HC, Stahn AC. Reduced vagal modulations of heart rate during overwintering in Antarctica. Sci Rep. 2020 Dec 11;10(1):21810. doi: 10.1038/s41598-020-78722-3.

  PMID: 33311648 BACKGROUND

• Stahn AC, Riemer M, Wolbers T, Werner A, Brauns K, Besnard S, Denise P, Kuhn S, Gunga HC. Spatial Updating Depends on Gravity. Front Neural Circuits. 2020 Jun 5;14:20. doi: 10.3389/fncir.2020.00020. eCollection 2020.

  PMID: 32581724 BACKGROUND

• Stahn AC, Gunga HC, Kohlberg E, Gallinat J, Dinges DF, Kuhn S. Brain Changes in Response to Long Antarctic Expeditions. N Engl J Med. 2019 Dec 5;381(23):2273-2275. doi: 10.1056/NEJMc1904905. No abstract available.

  PMID: 31800997 BACKGROUND

• Stahn AC, Werner A, Opatz O, Maggioni MA, Steinach M, von Ahlefeld VW, Moore A, Crucian BE, Smith SM, Zwart SR, Schlabs T, Mendt S, Trippel T, Koralewski E, Koch J, Chouker A, Reitz G, Shang P, Rocker L, Kirsch KA, Gunga HC. Increased core body temperature in astronauts during long-duration space missions. Sci Rep. 2017 Nov 23;7(1):16180. doi: 10.1038/s41598-017-15560-w.

  PMID: 29170507 BACKGROUND

• Strewe C, Moser D, Buchheim JI, Gunga HC, Stahn A, Crucian BE, Fiedel B, Bauer H, Gossmann-Lang P, Thieme D, Kohlberg E, Chouker A, Feuerecker M. Sex differences in stress and immune responses during confinement in Antarctica. Biol Sex Differ. 2019 Apr 16;10(1):20. doi: 10.1186/s13293-019-0231-0.

  PMID: 30992051 BACKGROUND

Related Links

• Reference article that does not have a pubmed ID yet "Head-Down Tilt Position, but Not the Duration of Bed Rest Affects Resting State Electrocortical Activity"

MeSH Terms

Interventions

Space Flight

Intervention Hierarchy (Ancestors)

Aviation; Transportation; Technology, Industry, and Agriculture

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This study will investigate 5 astronauts on 6-month ISS missions, 2 astronauts on 12-month ISS missions, and 7 control subjects that are matched to astronauts and investigated at similar time points.

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: April 23, 2021
• Study Start: August 1, 2021
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: October 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); DE (1)