The Impact of 6 and 12 Months in Space on Human Brain Structure and Intracranial Fluid Shifts

Abstract As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month (n = 2 astronauts) versus 6-month (n = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with long-duration spaceflight and demonstrate the need for closer study of fluid shifts.

† Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf            Figure S2. Correlations of Slope of Brain Changes with Inter-Mission Time. Figure S2 Legend. Graphs are shown for the three regions that showed significant correlations for this relationship. Inter-mission time is calculated as the time from the previous flight's landing day to the launch day of the present flight. Individual data points are not shown to protect astronaut privacy. For visual reference, linear model (green line) and 95% confidence interval (green shading) are shown.

Figure S4
Legend. Graphs are shown for the four significant correlations between preflight ventricular volume and past flight experience. Individual data points are not shown to protect astronaut privacy. For visual reference, linear model (green line) and 95% confidence interval (green shading) are shown.

Less time between missions
Greater preflight ventricular volume   (Bernard and Seidler 2013), we used the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) toolbox (Diedrichsen and others 2009). SUIT atlas also includes the vermis, but the CERES atlas does not, so we have not included any vermal ROIs in the present work. -3.52 6.4x controls -3.0x 6-month ✝ p < 0.10; *p < 0.05; **p < 0.01; ***p < 0.001. FW = free water; GMv = gray matter volume; CT = cortical thickness.

More previous missions
a The left panel presents the median slope of brain changes with normal aging, in units of change per year, for the T1 and dMRI control groups, as well as the median slope of brain changes, in units of change per year, from pre-to postflight for the 6-month astronauts. In parentheses under each median slope is the interquartile range (IQR) for that slope. W and p values are presented for the results of a nonparametric Wilcoxon signed-rank test for between-group differences in slope values.
b For qualitative comparison, the right panel presents the slope values for each of the 12-month astronauts and a percentage comparison to the 6-month and control groups using the formula: (12-month astronaut brain value) / (median 6-month or control group brain value). The right side of the table calculates the percent recovery at six months (i.e., at the Return+180 days postflight scan) for the 6-month astronauts and for the two 12-month astronauts. Percent recovery by six months postflight was calculated using the formula: ((Return+5 days value -Return+180 days value) / (Return+5 days value) * 100%) on the values of percentage change from baseline. 6-month astronauts for whom no recovery occurred (e.g., continued ventricular volume increase postflight) were not included in the recovery percentage calculation. Recovery values that omitted any 6-month astronauts are indicated with a superscript and described in more detail below. Italics for the 12-month recovery percentages indicate no recovery and are elaborated in the footnotes below. The 6-month astronaut who dropped out before the R+180 time point was omitted from all recovery calculations.
c Left lateral ventricle volume: Recovery percentage includes n=4 six-month astronauts who showed a pattern of recovery. n=5 six-month astronauts showed continued increases (+4.39 ± 3.19%) at R+180 and were not included in the recovery percentage.
d Right lateral ventricle volume: Recovery percentage includes n=5 six-month astronauts who showed a pattern of recovery. n=4 six-month astronauts showed continued increases (+6.87 ± 2.41%) at R+180 and were not included in the recovery percentage.
e Right precentral gyrus FW: Recovery percentage includes n=8 six-month astronauts who showed a pattern of recovery; all of these individuals and both 12-month astronauts showed recovery >100%. n=1 six-month astronaut showed continued decreases (-0.22%) at R+180 and was not included in the recovery percentage.
f Right postcentral gyrus FW: Recovery percentage includes n=8 six-month astronauts who showed a pattern of recovery; n=7 of these individuals and one of the 12-month astronauts showed recovery >100%. n=1 six-month astronaut showed continued increases (+4.34%) at R+180 and was not included in the recovery percentage.
g Right SMA FW: Recovery percentage includes n=7 six-month astronauts who showed a pattern of recovery; n=6 of these individuals and one of the 12-month astronauts showed recovery >100%. n=2 six-month astronauts showed continued increases (+2.94%) or decreases (-6.00%) at R+180 and were not included in the recovery percentage.
h Right frontal pole FW: Recovery percentage includes n=6 six-month astronauts who showed a pattern of recovery; n=1 of these individuals showed recovery >100%. n=3 six-month astronauts showed continued increases (+2.72%, +5.68%, +14.72%) at R+180 and were not included in the recovery percentage.
j Right precentral gyrus CT: Recovery percentage includes n=6 six-month astronauts who showed a pattern of recovery. n=3 six-month astronauts showed continued increases (+1.34%, +5.63%) or continued decreases (-2.39%) at R+180 and were not included in the recovery percentage.
k Right postcentral gyrus GMv: Recovery percentage includes n=7 six-month astronauts who showed a pattern of recovery; n=4 of these individuals showed recovery >100%. n=2 six-month astronauts showed continued decreases (-0.66%, -1.89%) at R+180 and were not included in the recovery percentage.
l Right postcentral gyrus CT: Recovery percentage includes n=8 six-month astronauts who showed a pattern of recovery; n=3 of these individuals and one of the 12-month astronauts showed recovery >100%. n=1 six-month astronaut showed continued decreases (-2.43%) at R+180 and was not included in the recovery percentage. m Right SMA GMv: Recovery percentage includes n=6 six-month astronauts who showed a pattern of recovery. n=3 sixmonth astronauts showed continued increases (+0.01%) or continued decreases (-1.00%, -3.31%) at R+180 and were not included in the recovery percentage. Here, one of the 12-month astronauts showed some recovery at R+30, but then continued increases (+1.28%) from R+30 to R+180. n Right frontal pole GMv: Recovery percentage includes n=7 six-month astronauts who showed a pattern of recovery; n=1 of these individuals and one of the 12-month astronauts showed recovery >100%. n=2 six-month astronauts showed continued increases (+3.36%) or decreases (-0.87) at R+180 and were not included in the recovery percentage. Here, one of the 12month astronauts showed little change from pre-to postflight, but continued increase (+0.59%) from R+5 to R+180. o Anterior cerebellum volume: Recovery percentage includes n=8 six-month astronauts who showed a pattern of recovery; n=6 of these individuals showed recovery >100%. n=1 six-month astronaut showed continued increases (+0.07%) at R+180 and was not included in the recovery percentage.
p Posterior cerebellum volume: Recovery percentage includes n=7 six-month astronauts who showed a pattern of recovery; n=5 of these individuals and both 12-month astronauts showed recovery >100%. n=2 six-month astronaut showed continued decreases (-0.65%, -0.61%) at R+180 and were not included in the recovery percentage.
q Left crus I volume: Recovery percentage includes n=8 six-month astronauts who showed a pattern of recovery; n=5 of these individuals and one of the 12-month astronauts showed recovery >100%. n=1 six-month astronaut showed continued decreases (-2.31%) at R+180 and was not included in the recovery percentage. r Left crus I volume: Recovery percentage includes n=6 six-month astronauts who showed a pattern of recovery; n=3 of these individuals and one of the 12-month astronauts showed recovery >100%. n=3 six-month astronaut showed continued increases (+1.68%, +0.51%) or continued decreases (-1.22%) at R+180 and were not included in the recovery percentage.  Movie S1-S2 Captions Movie S1. Ventricular Volume Increases with Flight. Clip depicts pre-versus postflight structural changes for TM-1 (i.e., the 12-month astronaut who showed substantial lateral ventricular volume increases with flight). Arrows indicate regions where ventricular volume increases are visible. Pre-and postflight structural images have been rigidly coregistered. The lack of movement of the skull bone between the two images demonstrates that this coregistration was successful and that pre-to post changes seen here are indeed brain changes and not related to poor registration or subject movement. To some observers, it might appear that these images depict a different slice for pre-and postflight scans; however, these perceived differences come from the fact that the ventricles have significantly expanded and the brain has shifted upwards within the skull with spaceflight. This has pushed on the surrounding tissue, making the pre-and postflight slices visually appear slightly different.
Movie S2. Gray Matter Compression at the Vertex. Clip depicts pre-versus postflight structural changes for TM-2 (i.e., the 12-month astronaut who showed sensorimotor gray matter volume increases with flight). Arrows indicate region of apparent compression of gray matter at the vertex related to postflight upward shift of the brain within the skull. Pre-and postflight structural images have been rigidly coregistered. The lack of movement of the skull bone between the two images demonstrates that this coregistration was successful and that pre-to post changes seen here are indeed brain changes and not related to poor registration or subject movement.