Brain Tissue–Volume Changes in Cosmonauts

Humans

To the Editor:

Long-duration spaceflight has detrimental effects in several physiological systems. Several studies have shown an upward shift of the cerebral hemispheres, a decrease in frontotemporal volume, and an increase in ventricle size after spaceflight.1-3 However, information is limited about the effects of microgravity on brain volume, particularly regarding changes that are evident more than 1 month after spaceflight.

We prospectively studied data from T1-weighted magnetic resonance imaging (MRI) that was performed in 10 male cosmonauts (mean age, 44 years; average space-mission duration, 189 days) at three time points: preflight (in 10 cosmonauts), short-term postflight (average, 9 days postflight; in 10), and long-term postflight follow-up (average, 209 days postflight; in 7). The volumes of gray matter, white matter, and cerebrospinal fluid (CSF) were analyzed with the use of voxel-based morphometry. (The complete methods and additional analyses are provided in the Supplementary Appendix, which is available with the full text of this letter at NEJM.org.) Aging effects that may occur over the interval between preflight and postflight were accounted for by longitudinal data from matched controls.

Figure 1. Figure 1. Brain-Volume Changes in Cosmonauts at Three Time Points.

Shown are topologic patterns of volume change in gray matter and cerebrospinal fluid (CSF) spaces in cosmonauts. Data are from MRI scans that were obtained preflight (in 10 cosmonauts), at short-term postflight (average, 9 days; in 10), and at long-term postflight follow-up (average, 209 days; in 7). White-matter changes are not shown. Panel A shows decreased gray-matter volume (dark blue) in the orbitofrontal and temporopolar regions postflight as compared with preflight. CSF volume for the same comparison is decreased under the vertex (light blue), while CSF volume is increased in the cerebral ventricles and basal cisterns (yellow-red). Panel B shows volume changes at long-term follow-up as compared with preflight. There is a persistent reduction in the gray-matter volume in the ventral cortical regions (dark blue) but less so than immediately postflight. Panel C shows increases in the gray-matter volume (pink) for these same regions at long-term follow-up as compared with short-term postflight. The CSF volume in the ventricles almost returned to preflight levels, but there was residual enlargement of the subarachnoid CSF space (yellow-red) surrounding the brain. This enlargement occurred after the return to Earth. Results were corrected for multiple comparisons after threshold-free cluster enhancement (TFCE) with the false discovery rate (P<0.05). Details of the methods of constructing these maps are provided in the Supplementary Appendix. L and R denote left and right, and A and P anterior and posterior.

The gray-matter volume postflight as compared with preflight showed a widespread decrease in the orbitofrontal and temporal cortexes; the maximal decrease was 3.3% in the right middle temporal gyrus. At long-term postflight follow-up, most reductions in gray-matter volume had recovered toward preflight levels (e.g., a 1.2% reduction in gray-matter volume persisted in the right temporal gyrus). The white-matter volume postflight as compared with preflight was reduced along a longitudinal tract of the left temporal lobe, but there was a global reduction of cerebral white-matter volume at long-term follow-up as compared with postflight. The ventral CSF spaces of the cerebral hemispheres and the ventricles had increased in volume postflight as compared with preflight (maximal increase, 12.9% in the third ventricle), while CSF volume below the vertex decreased. At long-term follow-up, the CSF volume in the ventricles had returned toward preflight values, while the CSF volume in the entire subarachnoid space around the brain had increased. Changes in the volumes of gray matter and CSF are shown in Figure 1.

The findings from an average of 7 months after a return to Earth can be summarized as showing that most of the loss in the gray-matter volume that was seen immediately postflight had recovered to preflight levels, while CSF volume continued to increase in the subarachnoid compartment. The expansion of CSF spaces in light of postflight decreases in the gray-matter volume and a reduction in the white-matter volume at follow-up suggests a persistent disturbance in CSF circulation even many months after a return to Earth. These brain-volume changes may relate to clinical findings, such as ocular and visual abnormalities after long-duration spaceflight.4,5 Future investigation is required in order to determine the overall clinical significance of the findings and to mitigate risks in long space missions.

Angelique Van Ombergen, Ph.D.
Steven Jillings, M.Sc.
Ben Jeurissen, Ph.D.
University of Antwerp, Antwerp, Belgium

Elena Tomilovskaya, Ph.D.
Institute of Biomedical Problems, Moscow, Russia

R. Maxine Rühl, M.D.
Ludwig-Maximilians-Universität München, Munich, Germany

Alena Rumshiskaya, M.D.
Federal Center of Treatment and Rehabilitation, Moscow, Russia

Inna Nosikova, M.D.
Institute of Biomedical Problems, Moscow, Russia

Liudmila Litvinova, M.Sc.
Federal Center of Treatment and Rehabilitation, Moscow, Russia

Jitka Annen, M.Sc.
University of Liège, Liège, Belgium

Ekaterina V. Pechenkova, Ph.D.
Research Institute of Neuropsychology of Speech and Writing, Moscow, Russia

Inessa B. Kozlovskaya, M.D., Ph.D.
Institute of Biomedical Problems, Moscow, Russia

Stefan Sunaert, M.D., Ph.D.
University of Leuven, Leuven, Belgium

Paul M. Parizel, M.D., Ph.D.
University of Antwerp, Antwerp, Belgium

Valentin Sinitsyn, M.D., Ph.D.
Lomonosov Moscow State University, Moscow, Russia

Steven Laureys, M.D., Ph.D.
University of Liège, Liège, Belgium

Jan Sijbers, Ph.D.
University of Antwerp, Antwerp, Belgium

Peter zu Eulenburg, M.D., Ph.D.
Ludwig-Maximilians-Universität München, Munich, Germany

Floris L. Wuyts, Ph.D.
University of Antwerp, Antwerp, Belgium

Supported by a grant (ISLRA-2009) from the European Space Agency, by Belgian Science Policy Office–Prodex, by a grant (63.1) from the Russian Academy of Sciences, by the University of Antwerp, by the University and University Hospital of Liège, by a grant (ARC-12/17-01) from the French Speaking Community Concerted Research Action, by grants (11U6414N, 11U6416N, and V400717N, to Dr. Van Ombergen; 12M3116N, to Dr. Jeurissen; and G084217N, to Dr. Sijbers) from the Research Foundation Flanders, by the Belgian National Funds for Scientific Research, by a grant (220020156.01) from the James McDonnell Foundation, by the IAP research network P7/06 of the Belgian government (Belgian Science Policy), by a grant (BMBF 01 EO 0901, to Dr. zu Eulenburg) from the German Federal Ministry of Education and Research, and by the 2016–2017 Amelia Earhart fellowship (to Dr. Van Ombergen) from Zonta International.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

Dr. Van Ombergen, Mr. Jillings, Dr. zu Eulenburg, and Dr. Wuyts contributed equally to this letter.

  1. 1. Koppelmans V, Bloomberg JJ, Mulavara AP, Seidler RD. Brain structural plasticity with spaceflight. NPJ Microgravity 2016;2:22.

  2. 2. Roberts DR, Albrecht MH, Collins HR, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. N Engl J Med 2017;377:17461753.

  3. 3. Alperin N, Bagci AM, Lee SH. Spaceflight-induced changes in white matter hyperintensity burden in astronauts. Neurology 2017;89:21872191.

  4. 4. Alperin N, Bagci AM. Spaceflight-induced visual impairment and globe deformations in astronauts are linked to orbital cerebrospinal fluid volume increase. Acta Neurochir Suppl 2018;126:215219.

  5. 5. Mader TH, Gibson CR, Pass AF, et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 2011;118:20582069.

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