Ophthalmic Changes in a Spaceflight Analog Are Associated with Brain Functional Reorganization

ABSTRACTImportanceFollowing long-duration missions onboard the International Space Station, some astronauts develop ophthalmic abnormalities collectively referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. SANS presents significant potential risk to astronaut health and performance; however, the origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies.ObjectiveTo investigate whether development of optic disc edema during a spaceflight analog impacts resting-state functional connectivity.Design, Setting and ParticipantsEleven healthy volunteers participated in this 58-day longitudinal study conducted at the :envihab facility at the German Aerospace Center.Interventions or ExposuresBaseline data were collected during a 14-day ambulatory phase in standard ambient air. All participants then underwent a spaceflight analog intervention: 30 days of strict head-down tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). The elevated CO2 level (0.5%) was matched to the hypercapnic environment of the International Space Station. The intervention was followed by a 14-day ambulatory recovery phase in standard ambient air. During the HDBR+CO2 spaceflight analog, 5 participants developed optic disc edema (SANS subgroup) and 6 did not (NoSANS group).Main Outcomes and MeasuresUsing functional magnetic resonance imaging (fMRI), we acquired resting-state data at 6 time points throughout the study: before (2), during (2), and after (2) the HDBR+CO2 intervention. We assessed the time course of resting-state functional connectivity changes from before, during, to after the HDBR+CO2, and contrasted longitudinal changes between the SANS and NoSANS subgroups. We also assessed if the SANS and NoSANS subgroups exhibited differential patterns of resting-state functional connectivity prior to the HDBR+CO2 intervention.ResultsThe SANS and NoSANS subgroups exhibited differential patterns of resting-state connectivity changes during the HDBR+CO2 spaceflight analog within visual and vestibular-related brain networks. We further found that the SANS and NoSANS subgroups exhibited differential resting-state brain activity prior to the spaceflight analog within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration.Conclusions and RelevanceSubgroup differences in resting-state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the HDBR+CO2 spaceflight analog. This finding suggests that SANS impacts not only neuro-ocular structures, but also brain function. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences.KEY POINTSQuestionDoes optic disc edema development during head-down tilt bed rest with elevated carbon dioxide impact brain resting-state functional connectivity?FindingsA subset of participants developed optic disc edema during the head-down tilt bed rest intervention with elevated ambient CO2. Participants who developed optic disc edema exhibited a distinct pattern of resting-state functional connectivity changes within visual and vestibular-related networks during the spaceflight analog compared to participants who did not. Participants who developed optic disc edema exhibited different resting-state brain activity prior to the spaceflight analog within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration.MeaningDevelopment of optic disc edema was associated with distinct patterns of brain resting-state functional connectivity during and prior to the spaceflight analog.