[en] The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.
Disciplines :
Neurology Neurosciences & behavior Space science, astronomy & astrophysics
Author, co-author :
Jillings, Steven; UA - University of Antwerp [BE] > Lab for Equilibrium Investigations and Aerospace
Pechenkova, Ekaterina; HSE University, Moscow > Laboratory for Cognitive Research
Tomilovskaya Elena; RAS - Russian Academy of Science [RU] > SSC RF - Institute for Biomedical Problem
Rukavishnikov, Ilya; RAS - Russian Academy of Science [RU] > SSC RF - Institute for Biomedical Problem
Jeurissen, Ben; UA - University of Antwerp [BE] > imec-Vision Lab
Van Ombergen, Angelique; UA - University of Antwerp [BE] > Lab for Equilibrium Investigations and Aerospace ; UA - University of Antwerp [BE] > Department of Translational Neuroscience - ENT
Nosikova, Inna; RAS - Russian Academy of Science [RU] > SSC RF - Institute for Biomedical Problem
Rumshiskaya, Alena; National Medical Research Treatment and Rehabilitation Center of the Ministry of Health of Russia > Radiology Department
Annen, Jitka ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group
De Laet, Chloë; UA - University of Antwerp [BE] > Lab for Equilibrium Investigations and Aerospace
Schoenmaeker, Catho; UA - University of Antwerp [BE] > Lab for Equilibrium Investigations and Aerospace
Sijbers, Jan; UA - University of Antwerp [BE] > imec-Vision Lab
Petrovichev, Victor; National Medical Research Treatment and Rehabilitation Center of the Ministry of Health of Russia > Radiology Department
Sunaert, Stefan; KU Leuven - Catholic University of Leuven [BE] > Department of Imaging & Pathology, Translational MRI
Parizel, Paul M; Royal Perth Hospital and University of Western Australia Medical School > Department of Radiology
Sinitsyn, Valentin; MSU - Lomonosov Moscow State University [RU] > Faculty of Fundamental Medicine
zu Eulenburg, Peter; LMU - Ludwig Maximilian University of Munich [DE] > Institute for Neuroradiology
Laureys, Steven ; Centre Hospitalier Universitaire de Liège - CHU > > Centre du Cerveau² ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group
Demertzi, Athina ✱; Université de Liège - ULiège > GIGA > GIGA CRC In vivo Imaging - Physiology of Cognition
Wuyts, Floris L ✱; UA - University of Antwerp [BE] > Lab for Equilibrium Investigations and Aerospace
✱ These authors have contributed equally to this work.
Language :
English
Title :
Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity
Publication date :
13 January 2023
Journal title :
Communications Biology
eISSN :
2399-3642
Publisher :
Nature, London, United Kingdom
Volume :
6
Pages :
46
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
H2020 - 945539 - HBP SGA3 - Human Brain Project Specific Grant Agreement 3
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] BELSPO - Belgian Science Policy Office [BE] ESA - European Space Agency [FR] FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE] RAS - Russian Academy of Sciences [RU] Fondation Léon Fredericq [BE] FERB - European Biomedical Research Foundation [IT] FRB - Fondation Roi Baudouin [BE] NSCF - National Natural Science Foundation of China [CN] Mind Care Foundation [BE] UE - Union Européenne [BE]
Pascual-Leone, A., Amedi, A., Fregni, F. & Merabet, L. B. The plastic human brain cortex. Annu. Rev. Neurosci. 28, 377–401 (2005).
Serfaty, C. A., Campello-Costa, P. & Linden, R. Rapid and long-term plasticity in the neonatal and adult retinotectal pathways following a retinal lesion. Brain Res. Bull. 66, 128–134 (2005).
Gaberova, K. et al. An individualized approach to neuroplasticity after early unilateral brain damage. Front. Psychiatry 10, 747 (2019).
Dayan, E. & Cohen, L. G. Neuroplasticity subserving motor skill learning. Neuron 72, 443–454 (2011).
Van Ombergen, A. et al. Brain tissue–volume changes in cosmonauts. N. Engl. J. Med. 379, 1678–1680 (2018).
Jillings, S. et al. Macro- and microstructural changes in cosmonauts’ brains after long-duration spaceflight. Sci. Adv. 6, (2020).
Lee, J. K. et al. Spaceflight-associated brain white matter microstructural changes and intracranial fluid redistribution. JAMA Neurol. 76, 412–419 (2019).
Roberts, D. R. et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. N. Engl. J. Med. 377, 1746–1753 (2017).
Alperin, N., Bagci, A. M. & Lee, S. H. Spaceflight-induced changes in white matter hyperintensity burden in astronauts. Neurology 89, 2187–2191 (2017).
Van Ombergen, A. et al. Brain ventricular volume changes induced by long-duration spaceflight. Proc. Natl Acad. Sci. USA 116, 10531–10536 Preprint at https://doi.org/10.1073/pnas.1820354116 (2019).
Koppelmans, V., Bloomberg, J. J., Mulavara, A. P. & Seidler, R. D. Brain structural plasticity with spaceflight. npj Microgravity 2, 2 (2016).
Kramer, L. A. et al. Intracranial effects of microgravity: a prospective longitudinal MRI study. Radiology 295, 640–648 (2020).
Demertzi, A. et al. Cortical reorganization in an astronaut’s brain after long-duration spaceflight. Brain Struct. Funct. 221, 2873–2876 Preprint at https://doi.org/10.1007/s00429-015-1054-3 (2016).
Van Ombergen, A. et al. Intrinsic functional connectivity reduces after first-time exposure to short-term gravitational alterations induced by parabolic flight. Sci. Rep. 7, 3061 (2017).
Pechenkova, E. et al. Alterations of functional brain connectivity after long-duration spaceflight as revealed by fMRI. Front. Physiol. 10, 761 (2019).
Hupfeld, K. E. et al. Brain and behavioral evidence for reweighting of vestibular inputs with long-duration spaceflight. Cereb. Cortex 10.1093/cercor/bhab239 (2021). DOI: 10.1093/cercor/bhab239
Van Ombergen, A. et al. The effect of spaceflight and microgravity on the human brain. J. Neurol. 264, 18–22 Preprint at https://doi.org/10.1007/s00415-017-8427-x (2017).
Leech, R. & Sharp, D. J. The role of the posterior cingulate cortex in cognition and disease. Brain 137, 12–32 (2014).
Raichle, M. E. et al. A default mode of brain function. Proc. Natl Acad. Sci. USA 98, 676–682 (2001).
Fransson, P. & Marrelec, G. The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. Neuroimage 42, 1178–1184 (2008).
Pearson, J. M., Heilbronner, S. R., Barack, D. L., Hayden, B. Y. & Platt, M. L. Posterior cingulate cortex: adapting behavior to a changing world. Trends Cogn. Sci. 15, 143–151 Preprint at https://doi.org/10.1016/j.tics.2011.02.002 (2011).
Parnaudeau, S., Bolkan, S. S. & Kellendonk, C. The mediodorsal thalamus: an essential partner of the prefrontal cortex for cognition. Biol. Psychiatry 83, 648–656 (2018).
Nelson, A. J. D. The anterior thalamic nuclei and cognition: a role beyond space? Neurosci. Biobehav. Rev. 126, 1–11 (2021).
Fiori, F., Candidi, M., Acciarino, A., David, N. & Aglioti, S. M. The right temporoparietal junction plays a causal role in maintaining the internal representation of verticality. J. Neurophysiol. 114, 2983–2990 Preprint at https://doi.org/10.1152/jn.00289.2015 (2015).
Ionta, S. et al. Multisensory mechanisms in temporo-parietal cortex support self-location and first-person perspective. Neuron 70, 363–374 (2011).
Kheradmand, A., Lasker, A. & Zee, D. S. Transcranial magnetic stimulation (TMS) of the supramarginal gyrus: a window to perception of upright. Cereb. Cortex 25, 765–771 (2015).
Senot, P. et al. When up is down in 0g: how gravity sensing affects the timing of interceptive actions. J. Neurosci. 32, 1969–1973 (2012).
Farrer, C. et al. The angular gyrus computes action awareness representations. Cereb. Cortex 18, 254–261 (2008).
Zwosta, K., Ruge, H. & Wolfensteller, U. Neural mechanisms of goal-directed behavior: outcome-based response selection is associated with increased functional coupling of the angular gyrus. Front. Hum. Neurosci. 9, 180 (2015).
van Kemenade, B. M. et al. Distinct roles for the cerebellum, angular gyrus, and middle temporal gyrus in action-feedback monitoring. Cereb. Cortex 29, 1520–1531 (2019).
Kelly, C. et al. A convergent functional architecture of the insula emerges across imaging modalities. Neuroimage 61, 1129–1142 (2012).
zu Eulenburg, P., Caspers, S., Roski, C. & Eickhoff, S. B. Meta-analytical definition and functional connectivity of the human vestibular cortex. Neuroimage 60, 162–169 (2012).
Craig, A. D. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666 Preprint at https://doi.org/10.1038/nrn894 (2002).
Craig, A. D. How do you feel—now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 Preprint at https://doi.org/10.1038/nrn2555 (2009).
Seeley, W. W. et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349–2356 (2007).
Medford, N. & Critchley, H. D. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response. Brain Struct. Funct. 214, 535–549 (2010).
Lackner, J. R. & Dizio, P. Space motion sickness. Exp. Brain Res. 175, 377–399 (2006).
Toschi, N. et al. Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions. Autonomic Neurosci. 202, 108–113 Preprint at 9
Napadow, V. et al. The brain circuitry underlying the temporal evolution of nausea in humans. Cereb. Cortex 23, 806–813 (2013).
Sclocco, R. et al. Brain circuitry supporting multi-organ autonomic outflow in response to nausea. Cereb. Cortex 26, 485–497 (2016).
Lopez, C. & Blanke, O. The thalamocortical vestibular system in animals and humans. Brain Res. Rev. 67, 119–146 (2011).
Wurthmann, S. et al. Cerebral gray matter changes in persistent postural perceptual dizziness. J. Psychosom. Res. 103, 95–101 (2017).
Riccelli, R. et al. Altered Insular and Occipital Responses to Simulated Vertical Self-Motion in Patients with Persistent Postural-Perceptual Dizziness. Front. Neurol. 8, Preprint https://doi.org/10.3389/fneur.2017.00529 (2017).
Lee, J.-O. et al. Altered brain function in persistent postural perceptual dizziness: a study on resting state functional connectivity. Hum. Brain Mapp. 39, 3340–3353 (2018).
Liao, Y. et al. Altered Baseline Brain Activity with 72 h of Simulated Microgravity – Initial Evidence from Resting-State fMRI. PLoS ONE 7, e52558 Preprint at https://doi.org/10.1371/journal.pone.0052558 (2012).
Liao, Y. et al. Altered Regional Homogeneity with Short-term Simulated Microgravity and Its Relationship with Changed Performance in Mental Transformation. PLoS ONE 8 e64931 Preprint at https://doi.org/10.1371/journal.pone.0064931 (2013).
Liao, Y. et al. The time course of altered brain activity during 7-day simulated microgravity. Front. Behav. Neurosci. 9, 124 (2015).
Zhou, Y. et al. Disrupted resting-state functional architecture of the brain after 45-day simulated microgravity. Front. Behav. Neurosci. 8, 200 (2014).
Cassady, K. et al. Effects of a spaceflight analog environment on brain connectivity and behavior. Neuroimage 141, 18–30 (2016).
McGregor, H. R. et al. Brain connectivity and behavioral changes in a spaceflight analog environment with elevated CO. Neuroimage 225, 117450 (2021).
Hupfeld, K. E. et al. Neural correlates of vestibular processing during a spaceflight analog with elevated carbon dioxide (CO): a pilot study. Front. Syst. Neurosci. 13, 80 (2019).
Roberts, D. R. et al. Cerebral Cortex Plasticity After 90 Days of Bed Rest: Data from TMS and fMRI. Aviat. Space Environ. Med. 81, 30–40 Preprint at https://doi.org/10.3357/asem.2532.2009 (2010).
Zeng, L.-L. et al. Default network connectivity decodes brain states with simulated microgravity. Cogn. Neurodyn. 10, 113–120 Preprint at https://doi.org/10.1007/s11571-015-9359-8 (2016).
Otsuka, K. et al. Anti-aging effects of long-term space missions, estimated by heart rate variability. Sci. Rep. 9, 8995 (2019).
Otsuka, K. et al. Circadian challenge of astronauts’ unconscious mind adapting to microgravity in space, estimated by heart rate variability. Sci. Rep. 8, 10381 (2018).
Thayer, J. F., Åhs, F., Fredrikson, M., Sollers, J. J. & Wager, T. D. A meta-analysis of heart rate variability and neuroimaging studies: Implications for heart rate variability as a marker of stress and health. Neurosci. Biobehav. Rev. 36, 747–756 Preprint at https://doi.org/10.1016/j.neubiorev.2011.11.009 (2012).
Trojan, S. & Pokorný, J. Theoretical aspects of neuroplasticity. Physiol. Res. 48, 87–97 (1999).
Draganski, B. & May, A. Training-induced structural changes in the adult human brain. Behav. Brain Res. 192, 137–142 Preprint at https://doi.org/10.1016/j.bbr.2008.02.015 (2008).
Gao, Q. et al. Altered dynamics of functional connectivity density associated with early and advanced stages of motor training in tennis and table tennis athletes. Brain Imaging Behav. 15, 1323–1334 (2021).
Miró-Padilla, A. et al. Sustained and transient gray matter volume changes after n-back training: a VBM study. Neurobiol. Learn. Mem. 178, 107368 (2021).
Koppelmans, V. et al. Cortical thickness of primary motor and vestibular brain regions predicts recovery from fall and balance directly after spaceflight. Brain Struct. Funct. 227, 2073–2086 (2022).
Roberts, D. R. et al. Prolonged microgravity affects human brain structure and function. Am. J. Neuroradiol. 40, 1878–1885 (2019).
Kahali, S., Raichle, M. E. & Yablonskiy, D. A. The role of the human brain neuron-glia-synapse composition in forming resting-state functional connectivity networks. Brain Sci. 11, 1565 (2021).
Kitamura, A. et al. Ingested d-aspartate facilitates the functional connectivity and modifies dendritic spine morphology in rat hippocampus. Cereb. Cortex 29, 2499–2508 (2019).
Roberts, D. R. et al. Altered cerebral perfusion in response to chronic mild hypercapnia and head-down tilt Bed rest as an analog for Spaceflight. Neuroradiology 63, 1271–1281 Preprint at https://doi.org/10.1007/s00234-021-02660-8 (2021).
Behzadi, Y., Restom, K., Liau, J. & Liu, T. T. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37, 90–101 (2007).
Martuzzi, R. et al. A whole-brain voxel based measure of intrinsic connectivity contrast reveals local changes in tissue connectivity with anesthetic without a priori assumptions on thresholds or regions of interest. Neuroimage 58, 1044–1050 (2011).
Yeo, B. T. T. et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J. Neurophysiol. 106, 1125–1165 (2011).
Tournier, J.-D. et al. MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. Neuroimage 202, 116137 (2019).
